U.S. patent application number 16/518513 was filed with the patent office on 2020-01-23 for methods of using a gip/glp1 co-agonist for therapy.
The applicant listed for this patent is Eli Lilly and Company. Invention is credited to Charles T. BENSON, Axel HAUPT, Melissa Kay THOMAS, Shweta URVA.
Application Number | 20200023040 16/518513 |
Document ID | / |
Family ID | 68387389 |
Filed Date | 2020-01-23 |
United States Patent
Application |
20200023040 |
Kind Code |
A1 |
BENSON; Charles T. ; et
al. |
January 23, 2020 |
METHODS OF USING A GIP/GLP1 CO-AGONIST FOR THERAPY
Abstract
The present invention provides a method for increasing glycemic
control in a patient in need thereof, by administering tirzepatide,
or a pharmaceutically acceptable salt thereof. The present
invention provides a method for improving weight management in a
patient in need thereof, by administering tirzepatide, or a
pharmaceutically acceptable salt thereof. Further providing a
method for treating a condition selected from atherosclerosis,
chronic kidney disease, NAFLD, and NASH. Further provided is a
method to prevent or induce remission of diabetes comprising
administration of tirzepatide, or a pharmaceutically acceptable
salt thereof. Further provided is a dosing regimen for increasing
glycemic control, improving weight management, and/or treating
dyslipidemia.
Inventors: |
BENSON; Charles T.;
(Zionsville, IN) ; HAUPT; Axel; (Zionsville,
IN) ; THOMAS; Melissa Kay; (Indianapolis, IN)
; URVA; Shweta; (Indianapolis, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Eli Lilly and Company |
Indianapolis |
IN |
US |
|
|
Family ID: |
68387389 |
Appl. No.: |
16/518513 |
Filed: |
July 22, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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62740619 |
Oct 3, 2018 |
|
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|
62730565 |
Sep 13, 2018 |
|
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62702061 |
Jul 23, 2018 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 3/10 20180101; A61P
3/04 20180101; A61P 13/12 20180101; A61K 38/26 20130101; A61P 9/10
20180101; A61P 1/16 20180101 |
International
Class: |
A61K 38/26 20060101
A61K038/26 |
Claims
1. A method of treating type 2 diabetes in a patient in need
thereof, comprising: administering an escalation dose about once
weekly for a minimum of at least about two weeks and thereafter
administering a maintenance dose about once weekly for a minimum of
at least about two weeks; wherein the escalation dose is selected
from the group consisting of about 2.5 mg, about 7.5 mg and about
12.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof; and wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 for treating type 2 diabetes in a patient
in need thereof, comprising: administering at least one escalation
dose about once weekly for a minimum of about four weeks and at
least one maintenance dose about once weekly for a minimum of about
four weeks following the escalation dose; wherein the escalation
dose is selected from the group consisting of about 2.5 mg, about
7.5 mg and about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; wherein the maintenance dose is selected
from the group consisting of about 5.0 mg, about 10.0 mg and about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof; and wherein the maintenance dose following an escalation
dose is a 2.5 mg increment.
3. The method of claim 1 or 2, wherein the escalation dose is about
2.5 mg and the maintenance dose is about 5.0 mg.
4. The method of claim 1 or 2, wherein the escalation dose is about
7.5 mg and the maintenance dose is about 10.0 mg.
5. The method of claim 1 or 2, wherein the escalation dose is about
12.5 mg and the maintenance dose is about 15.0 mg.
6. A method of improving glycemic control in a patient in need
thereof, comprising: administering an escalation dose about once
weekly for a minimum of at least about two weeks and thereafter
administering a maintenance dose about once weekly for a minimum of
at least about two weeks; wherein the escalation dose is selected
from the group consisting of about 2.5 mg, about 7.5 mg and about
12.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof; and wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 of improving glycemic control in a patient
in need thereof, comprising: administering an escalation dose about
once weekly for a minimum of about four weeks and thereafter
administering a maintenance dose about once weekly for a minimum of
about four weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is about a 2.5 mg
incremental increase relative to that escalation dose.
8. The method of claim 6 or 7, wherein the escalation dose is about
2.5 mg and the maintenance dose is about 5.0 mg.
9. The method of claim 6 or 7, wherein the escalation dose is about
7.5 mg and the maintenance dose is about 10.0 mg.
10. The method of claim 6 or 7, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
11. A method to induce remission or regression of diabetes, in a
patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of at least about two weeks
and thereafter administering a maintenance dose about once weekly
for a minimum of at least about two weeks; wherein the escalation
dose is selected from the group consisting of about 2.5 mg, about
7.5 mg and about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose is
selected from the group consisting of about 5.0 mg, about 10.0 mg
and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof.
12. The method of claim 11 to induce remission or regression of
diabetes, in a patient in need thereof, comprising: administering
at least one escalation dose about once weekly for a minimum of
about four weeks and at least one maintenance dose about once
weekly for a minimum of about four weeks following the escalation
dose; wherein the escalation dose is selected from the group
consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
increment.
13. The method of claim 11 or 12, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
14. The method of claim 11 or 12, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
15. The method of claim 11 or 12, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
16. A method to prevent diabetes, in a patient in need thereof,
comprising: administering an escalation dose about once weekly for
a minimum of at least about two weeks and thereafter administering
a maintenance dose about once weekly for a minimum of at least
about two weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose is selected from the group consisting
of about 5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof.
17. The method of claim 16 to prevent diabetes, in a patient in
need thereof, comprising: administering at least one escalation
dose about once weekly for a minimum of about four weeks and at
least one maintenance dose about once weekly for a minimum of about
four weeks following the escalation dose; wherein the escalation
dose is selected from the group consisting of about 2.5 mg, about
7.5 mg and about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; wherein the maintenance dose is selected
from the group consisting of about 5.0 mg, about 10.0 mg and about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof; and wherein the maintenance dose following an escalation
dose is a 2.5 mg increment.
18. The method of claim 16 or 17, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
19. The method of claim 16 or 17, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
20. The method of claim 16 or 17, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
21. A method to improve weight management, in a patient in need
thereof, comprising: administering an escalation dose about once
weekly for a minimum of at least about two weeks and thereafter
administering a maintenance dose about once weekly for a minimum of
at least about two weeks; wherein the escalation dose is selected
from the group consisting of about 2.5 mg, about 7.5 mg and about
12.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof; and wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof.
22. The method of claim 21 to improve weight management, in a
patient in need thereof, comprising: administering at least one
escalation dose about once weekly for a minimum of about four weeks
and at least one maintenance dose about once weekly for a minimum
of about four weeks following the escalation dose; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg increment.
23. The method of claim 21 or 22, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
24. The method of claim 21 or 22, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
25. The method of claim 21 or 22, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
26. A method for treating chronic kidney disease, comprising
administering an effective amount of tirzepatide or a
pharmaceutically acceptable salt thereof, to a patient in need of
such treatment.
27. The method of claim 26, for treating chronic kidney disease in
a patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of at least about two weeks
and thereafter administering a maintenance dose about once weekly
for a minimum of at least about two weeks; wherein the escalation
dose is selected from the group consisting of about 2.5 mg, about
7.5 mg and about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose is
selected from the group consisting of about 5.0 mg, about 10.0 mg
and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof.
28. The method of claim 26 for treating chronic kidney disease in a
patient in need thereof, comprising: administering at least one
escalation dose about once weekly for a minimum of about four weeks
and at least one maintenance dose about once weekly for a minimum
of about four weeks following the escalation dose; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, and wherein the maintenance dose following
an escalation dose is a 2.5 mg increment.
29. The method of claim 27 or 28, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
30. The method of claim 27 or 28, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
31. The method of claim 27 or 28, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
32. A method for treating atherosclerosis, comprising administering
an effective amount of tirzepatide or a pharmaceutically acceptable
salt thereof, to a patient in need of such treatment.
33. The method of claim 32 for treating atherosclerosis in a
patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of at least about two weeks
and thereafter administering a maintenance dose about once weekly
for a minimum of at least about two weeks; wherein the escalation
dose is selected from the group consisting of about 2.5 mg, about
7.5 mg and about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose is
selected from the group consisting of about 5.0 mg, about 10.0 mg
and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof.
34. The method of claim 32 for treating atherosclerosis in a
patient in need thereof, comprising: administering at least one
escalation dose about once weekly for a minimum of about four weeks
and at least one maintenance dose about once weekly for a minimum
of about four weeks following the escalation dose; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, and wherein the maintenance dose following
an escalation dose is a 2.5 mg increment.
35. The method of claim 33 or 34, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
36. The method of claim 33 or 34, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
37. The method of claim 33 or 34, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
38. A method for treating nonalcohol fatty liver disease,
comprising: administering an effective amount of tirzepatide or a
pharmaceutically acceptable salt thereof to a patient in need of
such treatment.
39. The method of claim 38 for treating nonalcohol fatty liver
disease, in a patient in need thereof, comprising: administering an
escalation dose about once weekly for a minimum of at least about
two weeks and thereafter administering a maintenance dose about
once weekly for a minimum of at least about two weeks; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose is selected from the group consisting of about 5.0
mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof.
40. The method of claim 38 for treating nonalcohol fatty liver
disease, in a patient in need thereof, comprising: administering at
least one escalation dose about once weekly for a minimum of about
four weeks and at least one maintenance dose about once weekly for
a minimum of about four weeks following the escalation dose;
wherein the escalation dose is selected from the group consisting
of about 2.5 mg, about 7.5 mg and about 12.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg increment.
41. The method of claim 39 or 40, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
42. The method of claim 39 or 40, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
43. The method of claim 39 or 40, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
44. A method for treating nonalcohol steatohepatitis, comprising:
administering an effective amount of tirzepatide or a
pharmaceutically acceptable salt thereof to a patient in need of
such treatment.
45. The method of claim 44 for treating nonalcohol steatohepatitis,
in a patient in need thereof, comprising administering an
escalation dose about once weekly for a minimum of at least about
two weeks and thereafter administering a maintenance dose about
once weekly for a minimum of at least about two weeks; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose is selected from the group consisting of about 5.0
mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof.
46. The method of claim 44 for treating nonalcohol steatohepatitis,
in a patient in need thereof, comprising: administering at least
one escalation dose about once weekly for a minimum of about four
weeks and at least one maintenance dose about once weekly for a
minimum of about four weeks following the escalation dose; wherein
the escalation dose is selected from the group consisting of about
2.5 mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg increment.
47. The method of claim 45 or 46, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
48. The method of claim 45 or 46, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
49. The method of claim 45 or 46, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
50. A method for treating obesity, in a patient in need thereof,
comprising: administering an escalation dose about once weekly for
a minimum of at least about two weeks and thereafter administering
a maintenance dose about once weekly for a minimum of at least
about two weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose is selected from the group consisting
of about 5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof.
51. The method of claim 50 for treating obesity, in a patient in
need thereof, comprising: administering at least one escalation
dose about once weekly for a minimum of about four weeks and at
least one maintenance dose about once weekly for a minimum of about
four weeks following the escalation dose; wherein the escalation
dose is selected from the group consisting of about 2.5 mg, about
7.5 mg and about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, wherein the maintenance dose is selected
from the group consisting of about 5.0 mg, about 10.0 mg and about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof; and wherein the maintenance dose following an escalation
dose is a 2.5 mg increment.
52. The method of claim 50 or 51, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
53. The method of claim 50 or 51, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
54. The method of claim 50 or 51, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
55. A method for treating diabetic kidney disease, in a patient in
need thereof, comprising: administering an escalation dose about
once weekly for a minimum of at least about two weeks and
thereafter administering a maintenance dose about once weekly for a
minimum of at least about two weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; and wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof.
56. The method of claim 55 for treating diabetic kidney disease, in
a patient in need thereof, comprising: administering at least one
escalation dose about once weekly for a minimum of about four weeks
and at least one maintenance dose about once weekly for a minimum
of about four weeks following the escalation dose; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, and wherein the maintenance dose following
an escalation dose is a 2.5 mg increment.
57. The method of claim 55 or 56, wherein the escalation dose is
about 2.5 mg and the maintenance dose is about 5.0 mg.
58. The method of claim 55 or 56, wherein the escalation dose is
about 7.5 mg and the maintenance dose is about 10.0 mg.
59. The method of claim 55 or 56, wherein the escalation dose is
about 12.5 mg and the maintenance dose is about 15.0 mg.
Description
[0001] The present invention provides methods of using novel doses
of a glucose-dependent insulinotropic polypeptide
(GIP)/glucagon-like peptide-1 (GLP1) dual agonist peptide,
tirzepatide, or a pharmaceutically acceptable salt thereof, to
treat type 2 diabetes (T2D). Also, the present invention provides
methods of using novel dosing regimens of a GIP/GLP1 dual agonist
peptide, tirzepatide, or a pharmaceutically acceptable salt
thereof, to treat type 2 diabetes. Furthermore, the present
invention provides novel medical uses for tirzepatide, or a
pharmaceutically acceptable salt thereof. More particularly, the
present invention provides a method for treating a condition
selected from the group of chronic kidney disease, atherosclerosis,
nonalcoholic fatty liver disease ("NAFLD"), and nonalcoholic
steatohepatitis ("NASH"). In a further embodiment, the present
invention provides a method for curing diabetes in certain
patients.
[0002] Diabetes mellitus is a chronic disorder characterized by
hyperglycemia resulting from defects in insulin secretion, insulin
action, or both. In T2D, the combined effects of impaired insulin
secretion and insulin resistance are associated with elevated blood
glucose levels.
[0003] U.S. Pat. No. 9,474,780 generally describes compositions
containing a GIP/GLP1 co-agonist, administered by parenteral
routes, and generally discloses a wide dosage range up to about 30
mg per person per week. U.S. Pat. No. 9,474,780 discloses the use
of GIP/GLP1 co-agonists for treating diabetes, obesity, and other
conditions. U.S. Pat. No. 9,474,780 describes and claims
tirzepatide.
[0004] It is well-known that GLP1 treatments are associated with
nausea, vomiting, and/or diarrhea. For example, one study reported
that all GLP-1 receptor agonist dosing regimens significantly
increased the incidence of gastrointestinal adverse events.
Diabetes Technol Ther. 2015 January; 17(1):35-42. Also, previous
clinical trials of a GIP/GLP1 co-agonist compound have been
performed and found that tolerability at high doses was limited by
gastrointestinal adverse events. Schmitt, C. et al.
"Pharmacodynamics, pharmacokinetics and safety of multiple
ascending doses of the novel dual glucose-dependent insulinotropic
polypeptide/glucagon-like peptide-1 agonist RG7697 in people with
type 2 diabetes mellitus." Diabetes Obes. Metab. 2017;
19:1436-1445. Portron, A. et al. "Pharmacodynamics,
Pharmacokinetics, Safety, and Tolerability of the Novel Dual
GIP/GLP-1 Agonist (RG7697) after Single Subcutaneous Administration
in Healthy Subjects." 2390-PUB, A624, ADA-2017; Portron, A. et al.
"Pharmacodynamics, pharmacokinetics, safety and tolerability of the
novel dual glucose-dependent insulinotropic
polypeptide/glucagon-like peptide-1 agonist RG7697 after single
subcutaneous administration in healthy subjects." Diabetes Obes.
Metab. 2017; 19:14446-1453. The dose limitation associated with
gastrointestinal adverse events may prevent dosing to the desired
effective dose, may compromise patient compliance with treatment,
and may limit the effectiveness of the treatment regimen.
[0005] There is a need for novel doses of tirzepatide to provide
desired glycemic control, as evidenced for example, by further
reductions of HbA1c, and/or weight loss, while maintaining an
acceptable profile of safety and adverse events. There is also a
need for a novel dosing regimen of tirzepatide to provide desired
glycemic control, as evidenced for example, by further reductions
of HbA1c, and/or weight loss, while maintaining an acceptable
profile of safety and adverse events. Also, there is a need for a
GIP/GLP1 dual agonist treatment option for a condition selected
from chronic kidney disease, atherosclerosis, NAFLD, and NASH.
Furthermore, there is a desire for a treatment to cure diabetes by
preventing, reducing severity of, or inducing remission of
diabetes. There is a desire for a treatment to reduce or delay
progression of diabetes.
[0006] The present invention provides novel tirzepatide dosing
regimens for use in the aforementioned therapies that include a
maintenance dose selected from the group consisting of: about 5.0
mg, about 10.0 mg and about 15.0 mg. In another embodiment, the
present invention provides novel dosing regimens that include an
escalation dose (i.e., a dose lower than the desired maintenance
dose) and a maintenance dose. In another embodiment, the present
invention provides novel dosing regimens that include one or more
escalation doses and one or more maintenance doses. The present
invention provides novel dosing regimens that include administering
at least one escalation dose about once weekly for a minimum of
about four weeks and thereafter at least one maintenance dose about
once weekly for a minimum of about four weeks. In certain
embodiment, the doses may be administered for about four weeks. In
certain embodiments, the doses may be administered for more than
about four weeks as determined by the nurse, patient and/or health
care provider. For example, a maintenance dose may be administered
for more than about four weeks. In certain embodiments of the
present invention a maintenance dose may be increased to the next
highest maintenance dose of the present invention if additional
glycemic control is needed with or without an intervening
escalation dose. For example, in one dosing regimen according to
the present invention, the escalation dose is about 2.5 mg and the
maintenance dose is about 5.0 mg. In another dosing regimen
according to the present invention, two escalation doses are about
2.5 mg and about 7.5 mg and the maintenance doses are about 5.0 mg
and 10.0 mg. In another aspect of the present invention, the
escalation doses are about 2.5 mg, about 7.5 mg and about 12.5 mg
and the maintenance doses are about 5.0 mg, about 10.0 mg and about
15.0 mg. Escalation doses include about 2.5 mg, about 7.5 mg and
about 12.5 mg. Maintenance doses include about 5.0 mg, about 10.0
mg and about 15.0 mg. An escalation dose of 2.5 mg may be the
initial dose, or starting dose, for the dosing regimen provided
herein. As used herein, the term "escalation" or "escalation
dose(s)" means a titration or titration dose, as described
herein.
[0007] Accordingly, the present invention provides a method of
treating type 2 diabetes in a patient in need thereof, comprising:
administering an escalation dose about once weekly for a minimum of
about four weeks and thereafter administering a maintenance dose
about once weekly for a minimum of about four weeks; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg incremental increase relative to
that escalation dose. An embodiment of the present invention is
thus a method of treating type 2 diabetes wherein the escalation
dose administered about once weekly for at least about four weeks
is about 2.5 mg and the maintenance dose administered about once
weekly for at least about four weeks is about 5.0 mg. A further
embodiment of the present invention is a method wherein the
escalation dose administered about once weekly for at least about
four weeks is about 7.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 10.0 mg. A
further embodiment of the present invention is a method wherein the
escalation dose administered about once weekly for at least about
four weeks is about 12.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 15.0 mg. A
further embodiment of the present invention is wherein after a
first maintenance dose has been administered for the at least about
four weeks, a second escalation dose is administered about once
weekly for at least about four weeks and thereafter a second
maintenance dose is administered about once weekly for at least
about four weeks. One such method thus includes escalation doses of
about 2.5 mg and about 7.5 mg and maintenance doses of about 5.0 mg
and about 10.0 mg. Another embodiment of the present invention is
one where after a second maintenance does has been administered for
the at least about four weeks, a third escalation dose is
administered about once weekly for at least about four weeks and
thereafter a third maintenance does is administered about once
weekly for at least about four weeks. One such method thus includes
escalation doses of about 2.5 mg, about 7.5 mg and about 12.5 mg
and maintenance doses of about 5.0 mg, about 10.0 mg and about 15.0
mg.
[0008] As noted above, in certain embodiments of the present
invention a maintenance dose may be increased to a subsequent
maintenance dose if additional glycemic control is needed with or
without an intervening escalation dose. Thus, the present invention
further provides a method of treating type 2 diabetes in a patient
in need thereof, comprising: administering an escalation dose of
about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks and
thereafter administering a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and, optionally
thereafter, administering a second maintenance dose of about 10.0
mg of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and,
optionally thereafter, administering a third maintenance dose of
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0009] In another aspect the present invention provides a method of
treating type 2 diabetes in a patient in need thereof, comprising:
[0010] a) administering to said patient a dose of about 2.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; [0011] b) increasing
the dose to a dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, and administering to said
patient about once weekly for a minimum of about four weeks; [0012]
c) increasing the dose to a dose of about 7.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, and administering to
said patient about once weekly for a minimum of about four weeks;
[0013] d) increasing the dose to a dose of about 10.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, and
administering to said patient about once weekly for a minimum of
about four weeks; [0014] e) increasing the dose to a dose of about
12.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, and administering to said patient about once weekly for a
minimum of about four weeks; and [0015] f) increasing the dose to a
dose of about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, and administering to said patient about
once weekly for a minimum of about four weeks.
[0016] In one aspect, the present invention provides a method of
treating type 2 diabetes in a patient in need thereof, comprising:
[0017] a) administering to said patient an escalation dose of about
2.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0018] b) administering to said patient a maintenance
dose of about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0019] In another aspect, the present invention provides a method
of treating type 2 diabetes in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0020] Another embodiment provides a method of treating type 2
diabetes in a patient in need thereof, comprising: [0021] a)
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0022] b) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0023] Another embodiment provides a method of treating type 2
diabetes in a patient in need thereof, comprising: [0024] a)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0025] b) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0026] In another aspect, the present invention provides a method
of treating type 2 diabetes in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0027] Another embodiment provides a method of treating type 2
diabetes in a patient in need thereof, comprising: [0028] a)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0029] b) administering to said patient a maintenance dose of about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0030] Another embodiment provides a method of treating type 2
diabetes in a patient in need thereof, comprising: [0031] a)
administering to said patient an escalation dose of about 12.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0032] b) administering to said patient a maintenance dose of about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0033] In another aspect, the present invention provides a method
treating type 2 diabetes in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0034] In another aspect, the present invention provides a method
of treating type 2 diabetes in a patient in need thereof,
comprising: [0035] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0036] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0037] c) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0038] d)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0039] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose.
[0040] In another aspect, the present invention provides a method
of treating type 2 diabetes in a patient in need thereof,
comprising: [0041] g) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0042] h) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0043] i) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0044] j)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly [0045] k) administering to said patient an
escalation dose of about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0046] l) administering
to said patient a maintenance dose of about 15.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks.
[0047] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose. In another aspect, the
present invention includes a method as described in the preceding
paragraph but which does not include administering the 12.5 mg
escalation dose. In another aspect, the present invention includes
a method as described in the preceding paragraph but which does not
include administering the 7.5 mg and 12.5 mg escalation doses.
[0048] Furthermore, the present invention provides a method of
improving glycemic control in a patient in need thereof,
comprising: administering at least one escalation dose about once
weekly for a minimum of about four weeks and at least one
maintenance dose about once weekly for a minimum of about four
weeks following the escalation dose; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof, and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose. An
embodiment of the present invention is thus a method of improving
glycemic control wherein the escalation dose administered about
once weekly for at least about four weeks is about 2.5 mg and the
maintenance dose administered about once weekly for at least about
four weeks is about 5.0 mg. A further embodiment of the present
invention is a method wherein the escalation dose administered
about once weekly for at least about four weeks is about 7.5 mg and
the maintenance dose administered about once weekly for at least
about four weeks is about 10.0 mg. A further embodiment of the
present invention is a method wherein the escalation dose
administered about once weekly for at least about four weeks is
about 12.5 mg and the maintenance dose administered about once
weekly for at least about four weeks is about 15.0 mg. A further
embodiment of the present invention is wherein after a first
maintenance dose has been administered for the at least about four
weeks, a second escalation dose is administered about once weekly
for at least about four weeks and thereafter a second maintenance
dose is administered about once weekly for at least about four
weeks. One such method thus includes escalation doses of about 2.5
mg and about 7.5 mg and maintenance doses of about 5.0 mg and about
10.0 mg. A further embodiment of the present invention is one where
after a second maintenance dose has been administered for the at
least about four weeks, a third escalation dose is administered
about once weekly for at least about four weeks and thereafter a
third maintenance does is administered about once weekly for at
least about four weeks. One such method thus includes escalation
doses of about 2.5 mg, about 7.5 mg and about 12.5 mg and
maintenance doses of about 5.0 mg, about 10.0 mg and about 15.0
mg.
[0049] As noted above, in certain embodiments of the present
invention a maintenance dose may be increased to a subsequent
maintenance dose if additional glycemic control is needed with or
without an intervening escalation dose. Thus, the present invention
further provides a method of improving glycemic control in a
patient in need thereof, comprising: administering an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks and thereafter administering a maintenance dose of about
5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and,
optionally thereafter, administering a second maintenance dose of
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and,
optionally thereafter, administering a third maintenance dose of
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0050] Furthermore, the present invention provides a method of
improving glycemic control in a patient in need thereof,
comprising: [0051] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0052] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0053] In another aspect the present invention provides a method of
improving glycemic control in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0054] Another embodiment provides a method of improving glycemic
control in a patient in need thereof comprising: [0055] a)
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0056] b) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0057] Another embodiment provides a method of improving glycemic
control in a patient in need thereof comprising: [0058] a)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0059] b) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0060] In another aspect the present invention provides a method of
improving glycemic control in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0061] Another embodiment provides a method of improving glycemic
control in a patient in need thereof comprising: [0062] a)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly [0063] b) administering to said patient a
maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0064] Another embodiment provides a method of improving glycemic
control in a patient in need thereof, comprising: [0065] a)
administering to said patient an escalation dose of about 12.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0066] b) administering to said patient a maintenance dose of about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0067] In another aspect the present invention provides a method of
improving glycemic control in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0068] In another aspect the present invention provides a method of
improving glycemic control in a patient in need thereof,
comprising: [0069] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0070] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0071] c) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0072] d)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and
thereafter
[0073] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose.
[0074] In another aspect, the present invention provides a method
of improving glycemic control in a patient in need thereof,
comprising: [0075] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0076] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0077] c) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0078] d)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0079] e) administering to said patient an escalation dose of about
12.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0080] f) administering to said patient a maintenance
dose of about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0081] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose. In another aspect, the
present invention includes a method as described in the preceding
paragraph but which does not include administering the 12.5 mg
escalation dose. In another aspect, the present invention includes
a method as described in the preceding paragraph but which does not
include administering the 7.5 mg and 12.5 mg escalation doses.
[0082] In a further embodiment, is a method for treating type 2
diabetes in a patient in need thereof, comprising: administering
tirzepatide, or a pharmaceutically acceptable salt thereof, in a
tirzepatide dosing regimen that comprises an initiation phase, at
least one escalation phase, and a maintenance phase; wherein the
initiation phase comprises administration of 2.5 mg tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for
at least about 2 to 4 weeks; wherein the escalation phase comprises
administration of a dose that is increased from the initiation
phase dose or prior escalation phase dose by about 2.5 mg per week
for at least about 2 to 4 weeks per escalation phase, wherein the
escalation dose increases by 2.5 mg during each escalation phase
until the maintenance phase is reached; and wherein the maintenance
phase is about once weekly administration of a dose selected from
the group consisting of about 5 mg, about 10 mg and about 15 mg
tirzepatide, or a pharmaceutically acceptable salt thereof.
[0083] Also, the present invention provides a method of improving
weight management in a patient in need thereof, comprising:
administering an escalation dose about once weekly for a minimum of
about four weeks and thereafter administering at least one
maintenance dose about once weekly for a minimum of about four
weeks; wherein the escalation dose is selected from the group
consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose. An
embodiment of the present invention is thus a method of improving
weight management wherein the escalation dose administered about
once weekly for at least about four weeks is about 2.5 mg and the
maintenance dose administered about once weekly for at least about
four weeks is about 5.0 mg. A further embodiment of the present
invention is a method wherein the escalation dose administered
about once weekly for at least about four weeks is about 7.5 mg and
the maintenance dose administered about once weekly for at least
about four weeks is about 10.0 mg. A further embodiment of the
present invention is a method wherein the escalation dose
administered about once weekly for at least about four weeks is
about 12.5 mg and the maintenance dose administered about once
weekly for at least about four weeks is about 15.0 mg. A further
embodiment of the present invention is wherein after a first
maintenance dose has been administered for the at least about four
weeks, a second escalation dose is administered about once weekly
for at least about four weeks and thereafter a second maintenance
dose is administered about once weekly for at least about four
weeks. One such method thus includes escalation doses of about 2.5
mg and about 7.5 mg and maintenance doses of about 5.0 mg and about
10.0 mg. Another embodiment of the present invention is one where
after a second maintenance does has been administered for the at
least about four weeks, a third escalation dose is administered
about once weekly for at least about four weeks and thereafter a
third maintenance does is administered about once weekly for at
least about four weeks. One such method thus includes escalation
doses of about 2.5 mg, about 7.5 mg and about 12.5 mg and
maintenance doses of about 5.0 mg, about 10.0 mg and about 15.0
mg.
[0084] As noted above, in certain embodiments of the present
invention a maintenance dose may be increased to a subsequent
maintenance dose if additional glycemic control is needed with or
without an intervening escalation dose. Thus, the present invention
further provides a method of improving weight management in a
patient in need thereof, comprising: administering an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks and thereafter administering a maintenance dose of about
5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and,
optionally thereafter, administering a second maintenance dose of
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and,
optionally thereafter, administering a third maintenance dose of
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0085] In yet another aspect, the present invention provides a
method of improving weight management in a patient in need thereof
comprising: [0086] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0087] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0088] In another aspect, the present invention provides a method
of improving weight management in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0089] Another embodiment provides a method of improving weight
management in a patient in need thereof, comprising: [0090] a)
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0091] b) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0092] Another embodiment provides a method of improving weight
management in a patient in need thereof, comprising: [0093] a)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0094] b) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0095] In another aspect, the present invention provides a method
of improving weight management in a patient in need thereof
comprising: administering to said patient a maintenance dose of
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0096] Another embodiment provides a method of improving weight
management in a patient in need thereof, comprising: [0097] a)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0098] b) administering to said patient a maintenance dose of about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0099] Another embodiment provides a method of improving weight
management in a patient in need thereof, comprising: [0100] a)
administering to said patient an escalation dose of about 12.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and [0101] b)
administering to said patient a maintenance dose of about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0102] In another aspect, the present invention provides a method
of improving weight management in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0103] In another aspect, the present invention provides a method
of improving weight management in a patient in need thereof,
comprising: [0104] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0105] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0106] c) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0107] d)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0108] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose.
[0109] In another aspect, the present invention provides a method
of improving weight management in a patient in need thereof,
comprising: [0110] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0111] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0112] c) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0113] d)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0114] e) administering to said patient an escalation dose of about
12.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0115] f) administering to said patient a maintenance
dose of about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0116] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose. In another aspect, the
present invention includes a method as described in the preceding
paragraph but which does not include administering the 12.5 mg
escalation dose. In another aspect, the present invention includes
a method as described in the preceding paragraph but which does not
include administering the 7.5 mg and 12.5 mg escalation doses.
[0117] Also, the present invention provides a method of treating
chronic kidney disease in a patient in need thereof, comprising:
administering am escalation dose about once weekly for a minimum of
about four weeks and thereafter administering a maintenance dose
about once weekly for a minimum of about four weeks; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg incremental increase relative to
that escalation dose. An embodiment of the present invention for a
method of treating chronic kidney disease wherein the escalation
dose administered about once weekly for at least about four weeks
is about 2.5 mg and the maintenance dose administered about once
weekly for at least about four weeks is about 5.0 mg. A further
embodiment of the present invention is a method wherein the
escalation dose administered about once weekly for at least about
four weeks is about 7.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 10.0 mg. A
further embodiment of the present invention is a method wherein the
escalation dose administered about once weekly for at least about
four weeks is about 12.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 15.0 mg. A
further embodiment of the present invention is wherein the
escalation doses administered about once weekly for at least about
four weeks are about 2.5 mg and about 7.5 mg and the maintenance
doses administered about once weekly for at least about four weeks
are about 5.0 mg and about 10.0 mg. A further embodiment of the
present invention is wherein the escalation doses administered
about once weekly for at least about four weeks are about 2.5 mg,
about 5.0 mg and about 7.5 mg and the maintenance doses
administered about once weekly for at least about four weeks are
about 5.0 mg, about 10.0 mg and about 15.0 mg.
[0118] Accordingly, the present invention provides a method of
treating chronic kidney disease in a patient in need thereof,
comprising: [0119] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0120] b) administering to said patient
about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0121] In another aspect, the present invention provides a method
of treating chronic kidney disease in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0122] Another embodiment provides a method of treating chronic
kidney disease in a patient in need thereof comprising: [0123] a)
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0124] b) administering to said patient about 10.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0125] Another embodiment provides a method of treating chronic
kidney disease in a patient in need thereof comprising: [0126] a)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0127] b) administering to said patient about 10.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0128] In another aspect, the present invention provides a method
of treating chronic kidney disease in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0129] Another embodiment provides a method of treating chronic
kidney disease in a patient in need thereof comprising: [0130] a)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0131] b) administering to said patient about 15.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0132] Another embodiment provides a method of treating chronic
kidney disease in a patient in need thereof, comprising: [0133] a)
administering to said patient an escalation dose of about 12.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly [0134] b) administering to said patient about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0135] In another aspect, the present invention provides a method
of treating chronic kidney disease in a patient in need thereof
comprising: administering to said patient a maintenance dose of
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0136] In another aspect, the present invention provides a method
of treating chronic kidney disease in a patient in need thereof,
comprising: [0137] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0138] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0139] c) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0140] d)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0141] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose.
[0142] In another aspect, the present invention provides a method
of treating chronic kidney disease in a patient in need thereof,
comprising: [0143] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0144] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly [0145]
c) administering to said patient an escalation dose of about 7.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0146] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0147] e) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0148] f) administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0149] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose. In another aspect, the
present invention includes a method as described in the preceding
paragraph but which does not include administering the 12.5 mg
escalation dose. In another aspect, the present invention includes
a method as described in the preceding paragraph but which does not
include administering the 7.5 mg and 12.5 mg escalation doses.
[0150] In a further embodiment, is a method for treating diabetic
kidney disease, in a patient in need thereof, comprising:
administering an escalation dose about once weekly for a minimum of
about four weeks and thereafter administering a maintenance dose
about once weekly for a minimum of about four weeks; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg incremental increase relative to
that escalation dose.
[0151] Also, the present invention provides a method of treating
atherosclerosis in a patient in need thereof, comprising:
administering an escalation dose about once weekly for a minimum of
about four weeks and thereafter administering a maintenance dose
about once weekly for a minimum of about four weeks; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg incremental increase relative to
that escalation dose. An embodiment of the present invention for a
method of treating atherosclerosis wherein the escalation dose
administered about once weekly for at least about four weeks is
about 2.5 mg and the maintenance dose administered about once
weekly for at least about four weeks is about 5.0 mg. A further
embodiment of the present invention is a method wherein the
escalation dose administered about once weekly for at least about
four weeks is about 7.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 10.0 mg. A
further embodiment of the present invention is a method wherein the
escalation dose administered about once weekly for at least about
four weeks is about 12.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 15.0 mg. A
further embodiment of the present invention is wherein the
escalation doses administered about once weekly for at least about
four weeks are about 2.5 mg and about 7.5 mg and the maintenance
doses administered about once weekly for at least about four weeks
are about 5.0 mg and about 10.0 mg. A further embodiment of the
present invention is wherein the escalation doses administered
about once weekly for at least about four weeks are about 2.5 mg,
about 5.0 mg and about 7.5 mg and the maintenance doses
administered about once weekly for at least about four weeks are
about 5.0 mg, about 10.0 mg and about 15.0 mg.
[0152] In a further aspect, the present invention provides a method
of treating atherosclerosis in a patient in need thereof,
comprising: [0153] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0154] b) administering to said patient
about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0155] In another aspect, the present invention provides a method
treating atherosclerosis in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0156] Another embodiment provides a method treating
atherosclerosis in a patient in need thereof comprising: [0157] a)
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0158] b) administering to said patient about 10.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0159] Another embodiment provides a method treating
atherosclerosis in a patient in need thereof comprising: [0160] a)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0161] b) administering to said patient about 10.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0162] In another aspect, the present invention provides a method
of treating atherosclerosis in a patient in need thereof,
comprising: administering to said patient a maintenance dose of
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0163] Another embodiment provides a method treating
atherosclerosis in a patient in need thereof comprising: [0164] a)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly [0165] b) administering to said patient about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0166] Another embodiment provides a method of treating
atherosclerosis in a patient in need thereof, comprising: [0167] a)
administering to said patient an escalation dose of about 12.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0168] b) administering to said patient about 15.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0169] In another aspect, the present invention provides a method
of treating atherosclerosis in a patient in need thereof
comprising: [0170] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0171] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0172] c) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0173] d)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0174] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose.
[0175] In another aspect, the present invention provides a method
of treating atherosclerosis in a patient in need thereof,
comprising: [0176] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0177] b) administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0178] c) administering
to said patient an escalation dose of about 7.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0179] d)
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0180] e) administering to said patient an escalation dose of about
12.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0181] f) administering to said patient a maintenance
dose of about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0182] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose. In another aspect, the
present invention includes a method as described in the preceding
paragraph but which does not include administering the 12.5 mg
escalation dose. In another aspect, the present invention includes
a method as described in the preceding paragraph but which does not
include administering the 7.5 mg and 12.5 mg escalation doses.
[0183] Also, the present invention provides a method of treating
NAFLD in a patient in need thereof, comprising: administering an
escalation dose about once weekly for a minimum of about four weeks
and thereafter administering a maintenance dose about once weekly
for a minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental relative to that escalation dose. An embodiment of
the present invention for a method for treating NAFLD wherein the
escalation dose administered about once weekly for at least about
four weeks is about 2.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 5.0 mg. A
further embodiment of the present invention is a method wherein the
escalation dose administered about once weekly for at least about
four weeks is about 7.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 10.0 mg. A
further embodiment of the present invention is a method wherein the
escalation dose administered about once weekly for at least about
four weeks is about 12.5 mg and the maintenance dose administered
about once weekly for at least about four weeks is about 15.0 mg. A
further embodiment of the present invention is wherein the
escalation doses administered about once weekly for at least about
four weeks are about 2.5 mg and about 7.5 mg and the maintenance
doses administered about once weekly for at least about four weeks
are about 5.0 mg and about 10.0 mg. A further embodiment of the
present invention is wherein the escalation doses administered
about once weekly for at least about four weeks are about 2.5 mg,
about 5.0 mg and about 7.5 mg and the maintenance doses
administered about once weekly for at least about four weeks are
about 5.0 mg, about 10.0 mg and about 15.0 mg.
[0184] Accordingly, the present invention provides a method of
treating NAFLD in a patient in need thereof, comprising: [0185] a)
administering to said patient an escalation dose of about 2.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0186] b) administering to said patient about 15.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0187] In another aspect, the present invention provides a method
of treating NAFLD in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0188] Another embodiment provides a method of treating NAFLD in a
patient in need thereof, comprising: [0189] a) administering to
said patient a maintenance dose of about 5.0 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0190] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0191] Another embodiment provides a method of treating NAFLD in a
patient in need thereof, comprising: [0192] a) administering to
said patient an escalation dose of about 7.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0193] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0194] In another aspect, the present invention provides a method
of treating NAFLD in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0195] Another embodiment provides a method of treating NAFLD in a
patient in need thereof, comprising: [0196] a) administering to
said patient a maintenance dose of about 10.0 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0197] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0198] Another embodiment provides a method of treating NAFLD in a
patient in need thereof, comprising: [0199] a) administering to
said patient an escalation dose of about 12.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly
[0200] b) administering to said patient about 15.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0201] In another aspect, the present invention provides a method
of treating NAFLD in a patient in need thereof, comprising:
administering to said patient a dose of about 15.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0202] In another aspect, the present invention provides a method
of treating NAFLD in a patient in need thereof, comprising: [0203]
a) administering to said patient an escalation dose of about 2.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0204] b) administering to said patient a maintenance dose of about
5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0205] c) administering to said patient an escalation
dose of about 7.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0206] d) administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0207] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose.
[0208] In another aspect, the present invention provides a method
of treating NAFLD in a patient in need thereof comprising: [0209]
a) administering to said patient an escalation dose of about 2.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0210] b) administering to said patient a maintenance dose of about
5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly [0211] c) administering to said patient
an escalation dose of about 7.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0212] d) administering
to said patient a maintenance dose of about 10.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0213] e)
administering to said patient an escalation dose of about 12.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0214] f) administering to said patient a maintenance dose of about
15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0215] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose. In another aspect, the
present invention includes a method as described in the preceding
paragraph but which does not include administering the 12.5 mg
escalation dose. In another aspect, the present invention includes
a method as described in the preceding paragraph but which does not
include administering the 7.5 mg and 12.5 mg escalation doses.
[0216] In an embodiment, is a method for treating dyslipidemia, in
a patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of about four weeks and
thereafter administering a maintenance dose about once weekly for a
minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose.
[0217] Also, the present invention provides a method of treating
NASH in a patient in need thereof, comprising: administering an
escalation dose about once weekly for a minimum of about four weeks
and thereafter administering a maintenance dose about once weekly
for a minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose. An
embodiment of the present invention for a method of treating NASH
wherein the escalation dose administered about once weekly for at
least about four weeks is about 2.5 mg and the maintenance dose
administered about once weekly for at least about four weeks is
about 5.0 mg. A further embodiment of the present invention is a
method wherein the escalation dose administered about once weekly
for at least about four weeks is about 7.5 mg and the maintenance
dose administered about once weekly for at least about four weeks
is about 10.0 mg. A further embodiment of the present invention is
a method wherein the escalation dose administered about once weekly
for at least about four weeks is about 12.5 mg and the maintenance
dose administered about once weekly for at least about four weeks
is about 15.0 mg. A further embodiment of the present invention is
wherein the escalation doses administered about once weekly for at
least about four weeks are about 2.5 mg and about 7.5 mg and the
maintenance doses administered about once weekly for at least about
four weeks are about 5.0 mg and about 10.0 mg. A further embodiment
of the present invention is wherein the escalation doses
administered about once weekly for at least about four weeks are
about 2.5 mg, about 5.0 mg and about 7.5 mg and the maintenance
doses administered about once weekly for at least about four weeks
are about 5.0 mg, about 10.0 mg and about 15.0 mg.
[0218] Accordingly, the present invention provides a method of
treating NASH in a patient in need thereof, comprising: [0219] a)
administering to said patient an escalation dose of about 2.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0220] b) administering to said patient about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0221] In another aspect the present invention provides a method of
treating NASH in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0222] Another embodiment provides a method of treating NASH in a
patient in need thereof, comprising: [0223] a) administering to
said patient a maintenance dose of about 5.0 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0224] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0225] Another embodiment provides a method of treating NASH in a
patient in need thereof, comprising: [0226] a) administering to
said patient an escalation dose of about 7.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0227] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0228] In another aspect, the present invention provides a method
of treating NASH in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0229] Another embodiment provides a method of treating NASH in a
patient in need thereof, comprising: [0230] a) administering to
said patient a maintenance dose of about 10.0 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0231] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0232] Another embodiment provides a method of treating NASH in a
patient in need thereof, comprising: [0233] a) administering to
said patient an escalation dose of about 12.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0234] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0235] In another aspect, the present invention provides a method
of treating NASH in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0236] In another aspect, the present invention provides a method
of treating NASH in a patient in need thereof, comprising: [0237]
a) administering to said patient an escalation dose of about 2.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0238] b) administering to said patient a maintenance dose of about
5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0239] c) administering to said patient an escalation
dose of about 7.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0240] d) administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0241] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose.
[0242] In another aspect, the present invention provides a method
of treating NASH in a patient in need thereof comprising: [0243] a)
administering to said patient an escalation dose of about 2.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0244] b) administering to said patient a maintenance dose of about
5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0245] c) administering to said patient an escalation
dose of about 7.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0246] d) administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0247] e) administering
to said patient an escalation dose of about 12.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0248] f)
administering to said patient a maintenance dose of about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0249] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose. In another aspect, the
present invention includes a method as described in the preceding
paragraph but which does not include administering the 12.5 mg
escalation dose. In another aspect, the present invention includes
a method as described in the preceding paragraph but which does not
include administering the 7.5 mg and 12.5 mg escalation doses.
[0250] Also, the present invention provides a method to cure
diabetes, induce remission or regression of diabetes, or prevent
diabetes in a patient in need thereof, comprising: administering an
escalation dose about once weekly for a minimum of about four weeks
and thereafter administering a maintenance dose about once weekly
for a minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose. An
embodiment of the present invention for a method to cure diabetes,
induce remission or regression of diabetes, or prevent diabetes
wherein the escalation dose administered about once weekly for at
least about four weeks is about 2.5 mg and the maintenance dose
administered about once weekly for at least about four weeks is
about 5.0 mg. A further embodiment of the present invention is a
method wherein the escalation dose administered about once weekly
for at least about four weeks is about 7.5 mg and the maintenance
dose administered about once weekly for at least about four weeks
is about 10.0 mg. A further embodiment of the present invention is
a method wherein the escalation dose administered about once weekly
for at least about four weeks is about 12.5 mg and the maintenance
dose administered about once weekly for at least about four weeks
is about 15.0 mg. A further embodiment of the present invention is
wherein the escalation doses administered about once weekly for at
least about four weeks are about 2.5 mg and about 7.5 mg and the
maintenance doses administered about once weekly for at least about
four weeks are about 5.0 mg and about 10.0 mg. A further embodiment
of the present invention is wherein the escalation doses
administered about once weekly for at least about four weeks are
about 2.5 mg, about 5.0 mg and about 7.5 mg and the maintenance
doses administered about once weekly for at least about four weeks
are about 5.0 mg, about 10.0 mg and about 15.0 mg.
[0251] Accordingly, the present invention provides a method to cure
diabetes, induce remission or regression of diabetes, or prevent
diabetes in a patient in need thereof, comprising: [0252] a)
administering to said patient an escalation dose of about 2.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0253] b) administering to said patient about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0254] In another aspect, the present invention provides a method
to cure diabetes, induce remission or regression of diabetes, or
prevent diabetes in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 5.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks.
[0255] Another embodiment provides a method to cure diabetes,
induce remission or regression of diabetes, or prevent diabetes in
a patient in need thereof, comprising: [0256] a) administering to
said patient a maintenance dose of about 5.0 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0257] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0258] Another embodiment provides a method to cure diabetes,
induce remission or regression of diabetes, or prevent diabetes in
a patient in need thereof, comprising: [0259] a) administering to
said patient an escalation dose of about 7.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0260] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0261] In another aspect, the present invention provides a method
to cure diabetes, induce remission or regression of diabetes, or
prevent diabetes in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 10.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0262] Another embodiment provides a method to cure diabetes,
induce remission or regression of diabetes, or prevent diabetes in
a patient in need thereof, comprising: [0263] a) administering to
said patient a maintenance dose of about 10.0 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0264] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0265] Another embodiment provides a method to cure diabetes,
induce remission or regression of diabetes, or prevent diabetes in
a patient in need thereof, comprising: [0266] a) administering to
said patient an escalation dose of about 12.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0267] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0268] In another aspect, the present invention provides a method
to cure diabetes, induce remission or regression of diabetes, or
prevent diabetes in a patient in need thereof, comprising:
administering to said patient a maintenance dose of about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0269] In another aspect, the present invention provides a method
to cure diabetes, induce remission or regression of diabetes, or
prevent diabetes in a patient in need thereof, comprising: [0270]
a) administering to said patient an escalation dose of about 2.5 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks; and thereafter
[0271] b) administering to said patient a maintenance dose of about
5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0272] c) administering to said patient an escalation
dose of about 7.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0273] d) administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0274] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose.
[0275] In another aspect, the present invention provides a method
to cure diabetes, induce remission or regression of diabetes, or
prevent diabetes in a patient in need thereof comprising: [0276] a)
administering to said patient an escalation dose of about 2.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0277] b) administering to said patient a maintenance dose of about
5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0278] c) administering to said patient an escalation
dose of about 7.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0279] d) administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0280] e) administering
to said patient an escalation dose of about 12.5 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0281] f)
administering to said patient a maintenance dose of about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof,
about once weekly for a minimum of about four weeks.
[0282] In another aspect, the present invention includes a method
as described in the preceding paragraph but which does not include
administering the 7.5 mg escalation dose. In another aspect, the
present invention includes a method as described in the preceding
paragraph but which does not include administering the 12.5 mg
escalation dose. In another aspect, the present invention includes
a method as described in the preceding paragraph but which does not
include administering the 7.5 mg and 12.5 mg escalation doses.
[0283] Furthermore, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating type 2 diabetes in a
patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of about four weeks and
thereafter administering a maintenance dose about once weekly for a
minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose.
[0284] The present invention provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating type 2 diabetes in a patient in need
thereof, comprising: [0285] a) administering to said patient an
escalation dose of about 2.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0286] b) administering
to said patient about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0287] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating type 2 diabetes in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0288] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating type 2 diabetes in a patient in need
thereof, comprising: [0289] a) administering to said patient a
maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0290] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0291] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating type 2 diabetes in a patient in need
thereof, comprising: [0292] a) administering to said patient an
escalation dose of about 7.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0293] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0294] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating type 2 diabetes in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0295] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating type 2 diabetes in a patient in need
thereof, comprising: [0296] a) administering to said patient a
maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0297] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0298] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in manufacture of a
medicament for treating type 2 diabetes in a patient in need
thereof, comprising: [0299] a) administering to said patient an
escalation dose of about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0300] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0301] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating type 2 diabetes in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0302] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating type 2 diabetes in a
patient in need thereof, comprising: [0303] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0304] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0305] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0306] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0307] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose.
[0308] In another aspect the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating type 2 diabetes in a
patient in need thereof, comprising: [0309] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0310] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0311] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0312] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0313] e) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0314] f) administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0315] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose. In another
aspect, the present invention includes a medicament as described in
the preceding paragraph but which does not include administering
the 12.5 mg escalation dose. In another aspect, the present
invention includes a medicament as described in the preceding
paragraph but which does not include administering the 7.5 mg and
12.5 mg escalation doses.
[0316] Furthermore, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament in improving glycemic control in a
patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of about four weeks and
thereafter administering a maintenance dose about once weekly for a
minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose.
[0317] Furthermore, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving glycemic control in a
patient in need thereof, comprising: [0318] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0319] b) administering
to said patient about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0320] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving glycemic control in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0321] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for improving glycemic control in a patient in need
thereof, comprising: [0322] a) administering to said patient an
escalation dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0323] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0324] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for improving glycemic control in a patient in need
thereof, comprising: [0325] a) administering to said patient an
escalation dose of about 7.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0326] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0327] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving glycemic control in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0328] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for improving glycemic control in a patient in need
thereof, comprising: [0329] a) administering to said patient a
maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0330] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0331] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for improving glycemic control in a patient in need
thereof, comprising: [0332] a) administering to said patient an
escalation dose of about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0333] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0334] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving glycemic control in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0335] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving glycemic control in a
patient in need thereof, comprising: [0336] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0337] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0338] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0339] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0340] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose.
[0341] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving glycemic control in a
patient in need thereof, comprising: [0342] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0343] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0344] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0345] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0346] e) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0347] f) administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0348] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose. In another
aspect, the present invention includes a medicament as described in
the preceding paragraph but which does not include administering
the 12.5 mg escalation dose. In another aspect, the present
invention includes a medicament as described in the preceding
paragraph but which does not include administering the 7.5 mg and
12.5 mg escalation doses.
[0349] Furthermore, present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament in improving weight management in a
patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of about four weeks and
thereafter administering a maintenance dose about once weekly for a
minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose.
[0350] In yet another aspect, the present invention provides a use
of tirzepatide, or a pharmaceutically acceptable salt thereof, in
the manufacture of a medicament for improving weight management in
a patient in need thereof, comprising: [0351] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0352] b) administering
to said patient about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0353] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving weight management in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0354] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for improving weight management in a patient in need
thereof, comprising: [0355] a) administering to said patient a
maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0356] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0357] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for improving weight management in a patient in need
thereof, comprising: [0358] a) administering to said patient an
escalation dose of about 7.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0359] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0360] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving weight management in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0361] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for improving weight management in a patient in need
thereof, comprising: [0362] a) administering to said patient a
maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0363] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0364] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for improving weight management in a patient in need
thereof, comprising: [0365] a) administering to said patient an
escalation dose of about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0366] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0367] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving weight management in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0368] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving weight management in a
patient in need thereof, comprising: [0369] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0370] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0371] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0372] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0373] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose.
[0374] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for improving weight management in a
patient in need thereof, comprising: [0375] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0376] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0377] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0378] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0379] e) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0380] f) administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0381] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose. In another
aspect, the present invention includes a medicament as described in
the preceding paragraph but which does not include administering
the 12.5 mg escalation dose. In another aspect, the present
invention includes a medicament as described in the preceding
paragraph but which does not include administering the 7.5 mg and
12.5 mg escalation doses.
[0382] Furthermore, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating chronic kidney disease in
a patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of about four weeks and
thereafter administering a maintenance dose about once weekly for a
minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose.
[0383] The present invention provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating chronic kidney disease in a patient in need
thereof, comprising: [0384] a) administering to said patient an
escalation dose of about 2.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0385] b) administering
to said patient about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0386] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating chronic kidney disease in
a patient in need thereof, comprising: administering to said
patient a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0387] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating chronic kidney disease in a patient in need
thereof, comprising: [0388] a) administering to said patient a
maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0389] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0390] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating chronic kidney disease in a patient in need
thereof, comprising: [0391] a) administering to said patient an
escalation dose of about 7.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0392] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0393] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating chronic kidney disease in
a patient in need thereof, comprising: administering to said
patient a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0394] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating chronic kidney disease in a patient in need
thereof, comprising: [0395] a) administering to said patient a
maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0396] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0397] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating chronic kidney disease in a patient in need
thereof, comprising: [0398] a) administering to said patient an
escalation dose of about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0399] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0400] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating chronic kidney disease in
a patient in need thereof, comprising: administering to said
patient a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0401] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating chronic kidney disease in
a patient in need thereof, comprising: [0402] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0403] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0404] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0405] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0406] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose.
[0407] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating chronic kidney disease in
a patient in need thereof, comprising: [0408] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0409] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
[0410] c) administering to said patient an escalation dose of about
7.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0411] d) administering to said patient a maintenance
dose of about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0412] e) administering to said patient
an escalation dose of about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0413] f) administering
to said patient a maintenance dose of about 15.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks.
[0414] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose. In another
aspect, the present invention includes a medicament as described in
the preceding paragraph but which does not include administering
the 12.5 mg escalation dose. In another aspect, the present
invention includes a medicament as described in the preceding
paragraph but which does not include administering the 7.5 mg and
12.5 mg escalation doses.
[0415] In a further embodiment, the present invention provides a
use of tirzepatide, or a pharmaceutically acceptable salt thereof,
in the manufacture of a medicament for treating diabetic kidney
disease in a patient in need thereof, comprising: administering an
escalation dose about once weekly for a minimum of about four weeks
and thereafter administering a maintenance dose about once weekly
for a minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose.
[0416] Furthermore, present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating atherosclerosis in a
patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of about four weeks and
thereafter administering a maintenance dose about once weekly for a
minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose.
[0417] Furthermore, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating atherosclerosis in a
patient in need thereof, comprising: [0418] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0419] b) administering
to said patient about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0420] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating atherosclerosis in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0421] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating atherosclerosis in a patient in need
thereof, comprising: [0422] a) administering to said patient a
maintenance dose of about 5.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0423] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0424] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating atherosclerosis in a patient in need
thereof, comprising: [0425] a) administering to said patient an
escalation dose of about 7.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0426] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0427] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating atherosclerosis in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0428] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating atherosclerosis in a patient in need
thereof, comprising: [0429] a) administering to said patient a
maintenance dose of about 10.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0430] b) administering
to said patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0431] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating atherosclerosis in a patient in need
thereof, comprising: [0432] a) administering to said patient an
escalation dose of about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and [0433] b) administering to said
patient about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0434] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating atherosclerosis in a
patient in need thereof, comprising: administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0435] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating atherosclerosis in a
patient in need thereof, comprising: [0436] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0437] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0438] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0439] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0440] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose.
[0441] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating atherosclerosis in a
patient in need thereof, comprising: [0442] a) administering to
said patient an escalation dose of about 2.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0443] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
[0444] c) administering to said patient an escalation dose of about
7.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0445] d) administering to said patient a maintenance
dose of about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0446] e) administering to said patient
an escalation dose of about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0447] f) administering
to said patient a maintenance dose of about 15.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks.
[0448] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose. In another
aspect, the present invention includes a medicament as described in
the preceding paragraph but which does not include administering
the 12.5 mg escalation dose. In another aspect, the present
invention includes a medicament as described in the preceding
paragraph but which does not include administering the 7.5 mg and
12.5 mg escalation doses.
[0449] In an embodiment is method of treating dyslipidemia in a
patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of at least about two weeks
and thereafter administering a maintenance dose about once weekly
for a minimum of at least about two weeks; wherein the escalation
dose is selected from the group consisting of about 2.5 mg, about
7.5 mg and about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose is
selected from the group consisting of about 5.0 mg, about 10.0 mg
and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof.
[0450] In an embodiment is a method for treating dyslipidemia in a
patient in need thereof, comprising: administering at least one
escalation dose about once weekly for a minimum of about four weeks
and at least one maintenance dose about once weekly for a minimum
of about four weeks following the escalation dose; wherein the
escalation dose is selected from the group consisting of about 2.5
mg, about 7.5 mg and about 12.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg increment.
[0451] In an embodiment is a method for treating dyslipidemia,
wherein the escalation dose is about 2.5 mg and the maintenance
dose is about 5.0 mg.
[0452] In an embodiment is a method for treating dyslipidemia,
wherein the escalation dose is about 7.5 mg and the maintenance
dose is about 10.0 mg.
[0453] In an embodiment is a method for treating dyslipidemia,
wherein the escalation dose is about 12.5 mg and the maintenance
dose is about 15.0 mg.
[0454] In an embodiment is a method for treating dyslipidemia,
further comprising an escalation dose of about 7.5 mg and a
maintenance dose of about 10.0 mg.
[0455] In an embodiment is a method for treating dyslipidemia,
further comprising an escalation dose of about 12.5 mg and a
maintenance dose of about 15.0 mg.
[0456] In an embodiment is a method for treating dyslipidemia,
wherein the patient in need of such treatment does not have
comorbid type 1 or type 2 diabetes.
[0457] Furthermore, present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NALFD in a patient in need
thereof, comprising: administering an escalation dose about once
weekly for a minimum of about four weeks and thereafter
administering a maintenance dose about once weekly for a minimum of
about four weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose.
[0458] In yet another aspect, the present invention provides a use
of tirzepatide, or a pharmaceutically acceptable salt thereof, in
the manufacture of a medicament for treating NAFLD in a patient in
need thereof, comprising: [0459] a) administering to said patient
an escalation dose of about 2.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0460] b) administering
to said patient about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0461] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NAFLD in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0462] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NAFLD in a patient in need thereof,
comprising: [0463] a) administering to said patient a maintenance
dose of about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0464] b) administering to said patient
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0465] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NAFLD in a patient in need thereof,
comprising: [0466] a) administering to said patient an escalation
dose of about 7.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0467] b) administering to said patient
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0468] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NAFLD in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0469] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NAFLD in a patient in need thereof,
comprising: [0470] a) administering to said patient a maintenance
dose of about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0471] b) administering to said patient
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0472] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NAFLD in a patient in need thereof,
comprising: [0473] a) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0474] b) administering to said patient
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0475] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NAFLD in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0476] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NAFLD in a patient in need
thereof, comprising: [0477] a) administering to said patient an
escalation dose of about 2.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0478] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0479] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0480] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0481] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose.
[0482] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NAFLD in a patient in need
thereof, comprising: [0483] a) administering to said patient an
escalation dose of about 2.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0484] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0485] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0486] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0487] e) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0488] f) administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0489] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose. In another
aspect, the present invention includes a medicament as described in
the preceding paragraph but which does not include administering
the 12.5 mg escalation dose. In another aspect, the present
invention includes a medicament as described in the preceding
paragraph but which does not include administering the 7.5 mg and
12.5 mg escalation doses.
[0490] Furthermore, present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NASH in a patient in need
thereof, comprising: administering an escalation dose about once
weekly for a minimum of about four weeks and thereafter
administering a maintenance dose about once weekly for a minimum of
about four weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose.
[0491] The present invention provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NASH in a patient in need thereof,
comprising: [0492] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0493] b) administering to said patient
about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0494] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NASH in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0495] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NASH in a patient in need thereof,
comprising: [0496] a) administering to said patient a maintenance
dose of about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0497] b) administering to said patient
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0498] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NASH in a patient in need thereof,
comprising: [0499] a) administering to said patient an escalation
dose of about 7.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0500] b) administering to said patient
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0501] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NASH in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0502] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NASH in a patient in need thereof,
comprising: [0503] a) administering to said patient a maintenance
dose of about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0504] b) administering to said patient
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0505] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating NASH in a patient in need thereof,
comprising: [0506] a) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0507] b) administering to said patient
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0508] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NASH in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0509] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NASH thereof, comprising:
[0510] a) administering to said patient an escalation dose of about
2.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0511] b) administering to said patient a maintenance
dose of about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0512] c) administering to said patient
an escalation dose of about 7.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0513] d) administering
to said patient a maintenance dose of about 10.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks.
[0514] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose.
[0515] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating NASH in a patient in need
thereof, comprising: [0516] a) administering to said patient an
escalation dose of about 2.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0517] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0518] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0519] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0520] e) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0521] f) administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0522] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose. In another
aspect, the present invention includes a medicament as described in
the preceding paragraph but which does not include administering
the 12.5 mg escalation dose. In another aspect, the present
invention includes a medicament as described in the preceding
paragraph but which does not include administering the 7.5 mg and
12.5 mg escalation doses.
[0523] Furthermore, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament to cure diabetes, induce remission or
regression of diabetes, or prevent diabetes in a patient in need
thereof, comprising: administering an escalation dose about once
weekly for a minimum of about four weeks and thereafter
administering a maintenance dose about once weekly for a minimum of
about four weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose.
[0524] The present invention provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament to cure diabetes, induce remission or regression of
diabetes, or prevent diabetes in a patient in need thereof,
comprising: [0525] a) administering to said patient an escalation
dose of about 2.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0526] b) administering to said patient
about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0527] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament to cure diabetes, induce remission or
regression of diabetes, or prevent diabetes in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0528] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament to cure diabetes, induce remission or regression of
diabetes, or prevent diabetes in a patient in need thereof,
comprising: [0529] a) administering to said patient a maintenance
dose of about 5.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly [0530] b) administering
to said patient about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0531] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament to cure diabetes, induce remission or regression of
diabetes, or prevent diabetes in a patient in need thereof,
comprising: [0532] a) administering to said patient an escalation
dose of about 7.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0533] b) administering to said patient
about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0534] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament to cure diabetes, induce remission or
regression of diabetes, or prevent diabetes in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0535] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament to cure diabetes, induce remission or regression of
diabetes, or prevent diabetes in a patient in need thereof,
comprising: [0536] a) administering to said patient a maintenance
dose of about 10.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0537] b) administering to said patient
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0538] Another embodiment provides a use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament to cure diabetes, induce remission or regression of
diabetes, or prevent diabetes in a patient in need thereof,
comprising: [0539] a) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0540] b) administering to said patient
about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0541] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament to cure diabetes, induce remission or
regression of diabetes, or prevent diabetes in a patient in need
thereof, comprising: administering to said patient a maintenance
dose of about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks.
[0542] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament to cure diabetes, induce remission or
regression of diabetes, or prevent diabetes in a patient in need
thereof, comprising: [0543] a) administering to said patient an
escalation dose of about 2.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0544] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0545] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0546] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks.
[0547] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose.
[0548] In another aspect, the present invention provides a use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament to cure diabetes, induce remission or
regression of diabetes, or prevent diabetes in a patient in need
thereof, comprising: [0549] a) administering to said patient an
escalation dose of about 2.5 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks; and thereafter [0550] b) administering
to said patient a maintenance dose of about 5.0 mg of tirzepatide,
or a pharmaceutically acceptable salt thereof, about once weekly
for a minimum of about four weeks; and thereafter [0551] c)
administering to said patient an escalation dose of about 7.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, about
once weekly for a minimum of about four weeks; and thereafter
[0552] d) administering to said patient a maintenance dose of about
10.0 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof, about once weekly for a minimum of about four weeks; and
thereafter [0553] e) administering to said patient an escalation
dose of about 12.5 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof, about once weekly for a minimum of about
four weeks; and thereafter [0554] f) administering to said patient
a maintenance dose of about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof, about once weekly for a
minimum of about four weeks.
[0555] In another aspect, the present invention includes a
medicament as described in the preceding paragraph but which does
not include administering the 7.5 mg escalation dose. In another
aspect, the present invention includes a medicament as described in
the preceding paragraph but which does not include administering
the 12.5 mg escalation dose. In another aspect, the present
invention includes a medicament as described in the preceding
paragraph but which does not include administering the 7.5 mg and
12.5 mg escalation doses.
[0556] An embodiment of the present invention for use in the
manufacture of a medicament described above is wherein the
escalation dose administered once weekly for four weeks is about
2.5 mg and the maintenance dose administered once weekly for four
weeks is about 5.0 mg. A further embodiment of the present
invention is wherein the escalation dose administered once weekly
for four weeks is about 7.5 mg and the maintenance dose
administered once weekly for four weeks is about 10.0 mg. A further
embodiment of the present invention is wherein the escalation dose
administered once weekly for four weeks is about 12.5 mg and the
maintenance dose administered once weekly for four weeks is about
15.0 mg. A further embodiment of the present invention is wherein
the escalation doses administered once weekly for four weeks are
about 2.5 mg and about 7.5 mg and the maintenance doses
administered once weekly for four weeks are about 5.0 mg and about
10.0 mg. A further embodiment of the present invention is wherein
the escalation doses administered once weekly for four weeks are
about 2.5 mg, about 5.0 mg and about 7.5 mg and the maintenance
doses administered once weekly for four weeks are about 5.0 mg,
about 10.0 mg and about 15.0 mg.
[0557] In embodiment 1a, is the use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for preventing diabetes in a patient in need thereof,
comprising: administering an escalation dose about once weekly for
a minimum of about two weeks and thereafter administering
maintenance dose about once weekly for a minimum of about two
weeks; wherein the escalation dose is selected from the group
consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose.
[0558] In embodiment 2a is the use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for preventing diabetes in a patient in need thereof,
comprising: administering an escalation dose about once weekly for
a minimum of about four weeks and thereafter administering a
maintenance dose about once weekly for a minimum of about four
weeks; wherein the escalation dose is selected from the group
consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof, wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is about a 5.0 mg
incremental increase relative to that escalation dose.
[0559] In embodiment 3a, is the use of embodiment 1a or 2a, wherein
the escalation dose is about 2.5 mg and the maintenance dose is
about 5.0 mg.
[0560] In embodiment 4a, is the use of embodiment 1a or 2a, wherein
the escalation dose is about 7.5 mg and the maintenance dose is
about 10.0 mg.
[0561] In embodiment 5a, is the use of embodiment 1a or 2a, wherein
the escalation dose is about 12.5 mg and the maintenance dose is
about 15.0 mg.
[0562] In embodiment 6a, is the use of embodiment 3a, further
comprising an escalation dose of about 7.5 mg and a maintenance
dose of about 10.0 mg.
[0563] In embodiment 7a, is the use of embodiment 6a, further
comprising an escalation dose of about 12.5 mg and a maintenance
dose of a bout 15.0 mg. In embodiment 8a, is the use of
tirzepatide, or a pharmaceutically acceptable salt thereof, in the
manufacture of a medicament for treating chronic kidney disease in
a patient in need thereof, comprising: administering an escalation
dose about once weekly for a minimum of about two weeks and
thereafter administering a maintenance dose about once weekly for a
minimum of about two weeks; wherein the escalation dose is selected
from the group consisting of about 2.5 mg, about 7.5 mg and about
12.5 mg of tirzepatide, or a pharmaceutically acceptable salt
thereof; wherein the maintenance dose is selected from the group
consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose.
[0564] In embodiment 9a, is the use of tirzepatide, or a
pharmaceutically acceptable salt thereof, in the manufacture of a
medicament for treating chronic kidney disease in a patient in need
thereof, comprising: administering at least one escalation dose
about once weekly for a minimum of about four weeks and at least
one maintenance dose about once weekly for a minimum of about four
weeks following the escalation dose; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is about
a 5.0 mg incremental increase relative to that escalation dose.
[0565] In embodiment 10a is the use of embodiment 8a or 9a, wherein
the escalation dose is about 2.5 mg and the maintenance dose is
about 5.0 mg.
[0566] In embodiment 11a is the use of embodiment 8a or 9a, wherein
the escalation dose is about 7.5 mg and the maintenance dose is
about 10.0 mg.
[0567] In embodiment 12a is the use of embodiment 8a or 9a, wherein
the escalation dose is about 12.5 mg and the maintenance dose is
about 15.0 mg.
[0568] In embodiment 13a is the use of embodiment 10a, further
comprising an escalation dose of about 7.5 mg and a maintenance
dose of about 10.0 mg.
[0569] In embodiment 14a the use of embodiment 13a, further
comprising an escalation dose of about 12.5 mg and a maintenance
dose of about 15.0 mg.
[0570] In another aspect the present invention provides
tirzepatide, or a pharmaceutically acceptable salt thereof, for use
in treating type 2 diabetes. In an embodiment the present invention
provides tirzepatide, or a pharmaceutically acceptable salt
thereof, for use in treating type 2 diabetes in a patient in need
thereof wherein: an escalation dose is administered about once
weekly for a minimum of about four weeks and thereafter a
maintenance dose is administered about once weekly for a minimum of
about four weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose. In another
aspect the present invention provides tirzepatide, or a
pharmaceutically acceptable salt thereof, for use in improving
glycemic control. In another aspect the present invention provides
tirzepatride, or a pharmaceutically acceptable salt thereof, for
use in improving glycemic control in a patient in need thereof
wherein: an escalation dose is administered about once weekly for a
minimum of about four weeks and thereafter a maintenance dose is
administered about once weekly for a minimum of about four weeks;
wherein the escalation dose is selected from the group consisting
of about 2.5 mg, about 7.5 mg and about 12.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg incremental increase relative to
that escalation dose. In another aspect the present invention
provides tirzepatide, or a pharmaceutically acceptable salt
thereof, for use in improving weight management. In another aspect
the present invention provides tirzepatride, or a pharmaceutically
acceptable salt thereof, for use in improving weight management in
a patient in need thereof wherein: an escalation dose is
administered about once weekly for a minimum of about four weeks
and thereafter a maintenance dose is administered about once weekly
for a minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose. In
another aspect the present invention provides tirzepatide, or a
pharmaceutically acceptable salt thereof, for use in treating
chronic kidney disease. In another aspect the present invention
provides tirzepatride, or a pharmaceutically acceptable salt
thereof, for use in treating chronic kidney disease in a patient in
need thereof wherein: an escalation dose is administered about once
weekly for a minimum of about four weeks and thereafter a
maintenance dose is administered about once weekly for a minimum of
about four weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose. In another
aspect the present invention provides tirzepatide, or a
pharmaceutically acceptable salt thereof, for use in treating
atherosclerosis. In another aspect the present invention provides
tirzepatride, or a pharmaceutically acceptable salt thereof, for
use in treating atherosclerosis in a patient in need thereof
wherein: an escalation dose is administered about once weekly for a
minimum of about four weeks and thereafter a maintenance dose is
administered about once weekly for a minimum of about four weeks;
wherein the escalation dose is selected from the group consisting
of about 2.5 mg, about 7.5 mg and about 12.5 mg of tirzepatide, or
a pharmaceutically acceptable salt thereof; wherein the maintenance
dose is selected from the group consisting of about 5.0 mg, about
10.0 mg and about 15.0 mg of tirzepatide, or a pharmaceutically
acceptable salt thereof; and wherein the maintenance dose following
an escalation dose is a 2.5 mg incremental increase relative to
that escalation dose. In another aspect the present invention
provides tirzepatide, or a pharmaceutically acceptable salt
thereof, for use in treating NAFLD. In another aspect the present
invention provides tirzepatride, or a pharmaceutically acceptable
salt thereof, for use in treating NAFLD in a patient in need
thereof wherein: an escalation dose is administered about once
weekly for a minimum of about four weeks and thereafter a
maintenance dose is administered about once weekly for a minimum of
about four weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose. In another
aspect the present invention provides tirzepatide, or a
pharmaceutically acceptable salt thereof, for use in treating NASH.
In another aspect the present invention provides tirzepatride, or a
pharmaceutically acceptable salt thereof, for use in treating NASH
in a patient in need thereof wherein: an escalation dose is
administered about once weekly for a minimum of about four weeks
and thereafter a maintenance dose is administered about once weekly
for a minimum of about four weeks; wherein the escalation dose is
selected from the group consisting of about 2.5 mg, about 7.5 mg
and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable
salt thereof; wherein the maintenance dose is selected from the
group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg
of tirzepatide, or a pharmaceutically acceptable salt thereof; and
wherein the maintenance dose following an escalation dose is a 2.5
mg incremental increase relative to that escalation dose. In
another aspect the present invention provides tirzepatide, or a
pharmaceutically acceptable salt thereof, for use in curing
diabetes, inducing remission or regression of diabetes, or
preventing diabetes. In another aspect the present invention
provides tirzepatride, or a pharmaceutically acceptable salt
thereof, for use in curing diabetes, inducing remission or
regression of diabetes, or preventing diabetes in a patient in need
thereof wherein: an escalation dose is administered about once
weekly for a minimum of about four weeks and thereafter a
maintenance dose is administered about once weekly for a minimum of
about four weeks; wherein the escalation dose is selected from the
group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of
tirzepatide, or a pharmaceutically acceptable salt thereof; wherein
the maintenance dose is selected from the group consisting of about
5.0 mg, about 10.0 mg and about 15.0 mg of tirzepatide, or a
pharmaceutically acceptable salt thereof; and wherein the
maintenance dose following an escalation dose is a 2.5 mg
incremental increase relative to that escalation dose.
[0571] An embodiment of the present invention for the uses
described above is wherein the escalation dose administered once
weekly for four weeks is about 2.5 mg and the maintenance dose
administered once weekly for four weeks is about 5.0 mg. A further
embodiment of the present invention is wherein the escalation dose
administered once weekly for four weeks is about 7.5 mg and the
maintenance dose administered once weekly for four weeks is about
10.0 mg. A further embodiment of the present invention is wherein
the escalation dose administered once weekly for four weeks is
about 12.5 mg and the maintenance dose administered once weekly for
four weeks is about 15.0 mg. A further embodiment of the present
invention is wherein the escalation doses administered once weekly
for four weeks are about 2.5 mg and about 7.5 mg and the
maintenance doses administered once weekly for four weeks are about
5.0 mg and about 10.0 mg. A further embodiment of the present
invention is wherein the escalation doses administered once weekly
for four weeks are about 2.5 mg, about 5.0 mg and about 7.5 mg and
the maintenance doses administered once weekly for four weeks are
about 5.0 mg, about 10.0 mg and about 15.0 mg.
[0572] As used herein, "titration dose" or "escalation dose" means
a dose that is less than the highest desired effective dose for the
patient. As used herein, the invention contemplates that a
"titration dose" or "escalation dose" may become the highest
desired effective dose, or "maintenance dose" if such dose is
observed to be the desired effective dose for the patient, and such
dose may be administered chronically for a period exceeding four
weeks.
[0573] As used herein "maintenance dose" means both a dose that is
the highest desired effective dose for the patient, and the
maintenance dose may become an escalation dose when such
maintenance dose is less than the desired highest effective dose.
That is to say, if, for a particular patient, the "about 5 mg"
maintenance dose contemplated by the present invention is not the
highest desired effective dose, then that 5 mg maintenance dose
will become, in retrospect, a titration dose as the particular
patient's dose will be increased up until reaching the next highest
maintenance dose contemplated by the present invention, e.g., 7.5
mg for at least about 2 weeks to 10 mg for at least about 2 weeks.
The invention contemplates that a patient that reaches a
maintenance dose of about 10 mg or about 15 mg may, as determined
by a physician or other health care provider, need to have their
dosage decreased to a lower maintenance dose.
[0574] Also provided herein is tirzepatide for use in simultaneous,
separate and sequential combinations with one or more agents
selected from metformin, a thiazolidinedione, a sulfonylurea, a
dipeptidyl peptidase 4 inhibitor, a sodium glucose co-transporter,
a SGLT-2 inhibitor, a growth differentiation factor 15 modulator
("GDF15"), a peptide tyrosine tyrosine modulator ("PYY"), a
modified insulin, amylin, a dual amylin calcitonin receptor
agonist, and oxyntomodulin agonist ("OXM") in the treatment of a
condition selected from the group consisting of type 2 diabetes,
chronic kidney disease, atherosclerosis, NALFD and NASH. Further
provided herein is a compound of the present invention for use in
simultaneous, separate and sequential combinations with one or more
agents selected from metformin, a thiazolidinedione, a
sulfonylurea, a dipeptidyl peptidase 4 inhibitor, a sodium glucose
co-transporter, a SGLT-2 inhibitor, GDF15, PYY, a modified insulin,
amylin, a dual amylin calcitonin receptor agonist, and OXM in the
improvement of glycemic control and/or weight management. Also
provided herein is a compound of the present invention for use in
simultaneous, separate and sequential combinations with one or more
agents selected from metformin, a thiazolidinedione, a
sulfonylurea, a dipeptidyl peptidase 4 inhibitor, a sodium glucose
co-transporter, a SGLT-2 inhibitor, GDF15, PYY, a modified insulin,
amylin, a dual amylin calcitonin receptor agonist, and OXM to cure
diabetes, induce remission or regression of diabetes, or prevent
diabetes. In an embodiment, a compound of the present invention is
provided in a fixed dose combination with one or more agents
selected from metformin, a thiazolidinedione, a sulfonylurea, a
dipeptidyl peptidase 4 inhibitor, a sodium glucose co-transporter,
a SGLT-2 inhibitor, GDF15, PYY, a modified insulin, amylin, a dual
amylin calcitonin receptor agonist, and OXM.
NAFLD and NASH Treatments
[0575] Nonalcoholic fatty liver disease ("NAFLD") is a liver
disease characterized by an accumulation of fat in the liver of
afflicted patients. Patients suffering from NAFLD may consume
little or no alcohol, and in an embodiment, the patient does not
have comorbid diabetes. NAFLD is a major cause of liver disease
worldwide. Younossi et. al. Global epidemiology of nonalcoholic
fatty liver disease-Meta-analytic assessment of prevalence,
incidence, and outcomes; Hepatology (July 2016) 64:1; 73-84.
Nonalcoholic steatohepatitis ("NASH") is a type of NAFLD with an
etiological constellation exhibiting macrovesicular hepatic
steatosis, inflammation, hepatocyte ballooning, and fibrosis. NASH
may lead to cirrhosis and liver failure. It has been established
that patients with NASH are more likely to develop cirrhosis, and
have a higher risk of cardiovascular mortality, and hepatocyte
carcinoma. This non-alcoholic, non-viral cirrhosis is, in fact,
among the top causes of liver transplantation.
[0576] NAFLD and NASH are progressive diseases characterized by the
development of liver fibrosis as NAFLD progresses to NASH. The
stage of NASH can be defined, for example, by the NASH CRN
(Clinical Research Network). Fibrosis staging measures the amount
and pattern of NASH fibrosis, as well as parenchymal architectural
remodeling in a patient. NASH is typically diagnosed in a human
patient using liver biopsy, and the diagnosis is predicted using
MRI-derived proton density fat fraction images ("MRI-PDFF"), plasma
cytokeratin 18 (CK18) fragment levels as a biomarker for hepatocyte
apoptosis, and plasma Pro-C3 (N-terminal type III collagen
propeptide) to predict fibrosis progression, and/or other
biomarkers. Vincent Wai-Sun Wong, et. al. Noninvasive biomarkers in
NAFLD and NASH--current progress and future promise; Nature Reviews
Gastroenterology & Hepatology; (29 May 2018). NAFLD, in which
excess lipid deposition occurs in the liver, is typically assessed
using imaging methods such as MRI-PDFF.
[0577] Currently, there is no approved pharmaceutical medicament
specifically for the treatment of NASH. Current NASH patient
recommendations include diet and exercise. There is a need for
pharmaceutical medicaments to offer additional treatment options
for patients suffering from NAFLD and NASH.
[0578] The present invention provides a method for treating NAFLD,
comprising administering an effective amount of tirzepatide or a
pharmaceutically acceptable salt thereof, to a patient in need of
such treatment. The present invention provides a method for
treating NASH, comprising administering an effective amount of
tirzepatide or a pharmaceutically acceptable salt thereof, to a
patient in need of such treatment. In an embodiment, the patient in
need of treatment for NASH has comorbid type 2 diabetes. In an
embodiment, the patient in need of treatment for NASH does not have
type 2 diabetes.
Chronic Kidney Disease Treatment
[0579] Chronic kidney disease ("CKD") is defined as abnormalities
of kidney structure or function, present for three months, with
implications for health of the patient. CKD can be classified on
the basis of the glomular filtration rate ("GFR") into five
categories. The GFR can be estimated using biomarkers, including
serum creatinine and albumin, albumin to creatinine ratio ("ACR"),
and serum cystatin C, Moderate CKD (GFR 30-59 mL/min/1.73 m2) is
classified as stage 3 CKD. In the adult population, a decreasing
GFR is associated with an increased cardiovascular disease ("CVD")
risk, independent of other cardiovascular ("CV") risk factors. The
CV mortality in patients with stage 3 and stage four CKD is
two-fold and three-fold higher, respectively, when compared with
patients with normal renal function. Patients with CKD and
established CVD have a much higher mortality rate compared with
patients with CVD and normal renal function. Therefore patients
with CKD are considered high risk (stage 3 CKD) or very high risk
(stage 4-5 CKD or on dialysis). Treatments for patients with CKD
typically include diet, exercise, cessation of smoking,
antihypertensive medications, and combinations of medications.
Desired treatments for CKD reduce inflammation, improve glycemic
control, and/or improve cellular function in such patients. There
is a desire for additional treatment options for patients with
CKD.
[0580] The present invention provides a method for treating CKD
comprising administering an effective amount of tirzepatide to a
patient in need thereof. In an embodiment, the treatment is for a
patient with Stage 3 CKD. In an embodiment, the treatment is for a
patient having Stage 4 CKD. In an embodiment, the treatment is for
a patient having Stage 2 CKD. In an embodiment, the treatment is
for a patient having Stage 1 CKD.
Atherosclerosis Treatment
[0581] Atherosclerosis is a condition that develops when plaque
builds up in the walls of the arteries. This buildup narrows the
arteries, impeding blood flow. Complications associated with
atherosclerosis and the atherosclerosis disease progression may
lead to a heart attack or stroke. Despite recent advancements in
treatment options, cardiovascular disease remains the leading cause
of death for people living with diabetes. The present invention
provides a method for treating atherosclerosis comprising
administering an effective amount of tirzepatide to a patient in
need thereof.
Cure Diabetes, Induce Remission or Regression of Diabetes, or
Prevent Diabetes
[0582] U.S. Pat. No. 9,474,780 teaches that tirzepatide is useful
for the treatment of diabetes, wherein "treating" includes
restraining, slowing, stopping, or reversing the progression or
severity of an existing symptom or disorder. Despite advances in
the treatment of diabetes, many patients receiving such treatment
are unable to reach their glycemic control goal or HbA1c goal.
[0583] U.S. Pat. No. 9,474,780 teaches that tirzepatide is useful
for the treatment of diabetes, wherein "treating" includes
restraining, slowing, stopping, or reversing the progression or
severity of an existing symptom or disorder. Despite advances in
the treatment of diabetes, many patients receiving such treatment
are unable to reach their glycemic control goal or HbA1c goal. This
invention provides a cure for diabetes wherein a patient receiving
treatment for diabetes using a tirzepatide dosing regimen
comprising a 2.5 mg tirzepatide once weekly start dose or
escalation dose is administered for four weeks and a 5.0 mg
tirzepatide once weekly maintenance dose is administered for at
least four weeks; if the patient does not achieve their HbA1c goal,
then an escalation dose of about 7.5 mg once weekly is administered
for at least four weeks and then a maintenance dose of 10.0 mg
tirzepatide once weekly is administered for at least four weeks;
wherein, if the patient does not achieve their HbA1c goal from at
least 4 weeks treatment using the 10.0 mg once weekly dose, then a
12.5 mg tirzepatide once weekly escalation dose may be administered
for at least 4 weeks, followed by a 15 mg once weekly maintenance
dose administered until the HbA1C goal is achieved for at least
about 2 weeks, and wherein such patient maintains their HbA1c goal
after cessation of all medications approved for use in the
treatment of diabetes or glycemic control. As used herein, the term
"diabetes medication," "diabetes medicine" and the like, means a
medication approved by the pertinent regulatory agency for use in
the treatment of glycemic control or Type II diabetes. In an
embodiment, the HbA1c measurement in the patient treated for
diabetes is less than or equal to about 5.9%. In an embodiment, the
patient maintains their HbA1c goal level for at least one month
without further tirzepatide administration. In an embodiment, the
patient previously treated for diabetes using tirzepatide maintains
their glycemic goal for at least one month without administration
of further tirzepatide or any other diabetes medication. In an
embodiment, the patient maintains their glycemic goal for at least
6 months without administration of further tirzepatide or any other
diabetes medication.
[0584] As used herein, the term "diabetes medication," "diabetes
medicine" and the like, means a medication approved by the
pertinent regulatory agency for use in the treatment of glycemic
control or Type II diabetes. In an embodiment, the HbA1c
measurement in the patient treated for diabetes is less than or
equal to about 5.9%. In an embodiment, the patient maintains their
HbA1c goal level for at least one month without further tirzepatide
administration. In an embodiment, the patient previously treated
for diabetes using tirzepatide maintains their glycemic goal for at
least one month without administration of further tirzepatide or
any other diabetes medication. In an embodiment, the patient
maintains their glycemic goal for at least 6 months without
administration of further tirzepatide or any other diabetes
medication.
[0585] The doses of the present invention are likely to have
specific concentrations of 5 mg/mL, 10 mg/mL, 15 mg/mL, 20 mg/mL,
25 mg/mL and 30 mg/mL. Such compositions may be presented in a
pre-filled syringe. Such pre-filled syringe may be useful for
administering one half milliliter of such composition per patient
per dose. The doses of the present invention are typically
administered subcutaneously. The doses are typically administered
using a pre-filled, disposable pen, reusable pen, or automatic pen
injector. In an embodiment, the device is an automatic injection
apparatus as claimed by U.S. Pat. No. 8,734,394.
[0586] As used herein, "tirzepatide" means a GIP/GLP1 dual agonist
peptide as described in U.S. Pat. No. 9,474,780 and described by
CAS Registry Number: 2023788-19-2. Tirzepatide is described in
Example 1 of U.S. Pat. No. 9,474,780, with the following sequence:
YX.sub.1EGTFTSDYSIX.sub.2LDKIAQKAFVQWLIAGGPSSGAPPPS
[0587] wherein X.sub.1 is Aib; X.sub.2 is Aib; K at position 20 is
chemically modified through conjugation to the epsilon-amino group
of the K side-chain with
(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl).sub.2-(.gamma.Glu).sub.1-CO--(CH.s-
ub.2).sub.18--CO.sub.2H; and the C-terminal amino acid is amidated
as a C-terminal primary amide (SEQ ID NO: 1).
[0588] As used herein, the term "administering" means the
administration by a nurse, health care provider, patient or any
other individual including self-administration. This includes not
only delivering into the body but also prescribing, dispensing or
assisting in any way with delivery.
[0589] As used herein, the term "increasing the dose", "increasing
the maintenance dose", "increasing the titration dose" and
"increasing the escalation dose" means the raising of the
respective dose by a nurse, health care provider, patient or any
other individual.
[0590] As used herein, "pharmaceutically acceptable salt" is well
known to the skilled artisan. In an embodiment is a
pharmaceutically acceptable salt that is a tirzepatide
trifluoroacetate salt. In an embodiment is tirzepatide as a
non-salt.
[0591] As used herein, the term "biomarker", means a laboratory
measurement that reflects the activity of a disease process.
Biomarkers may be used to diagnose a disease or condition, and
usually quantitatively correlate (either directly or inversely)
with disease progression. In the clinical trial setting, a
biomarker is a measure of the effect of a specific treatment that
may correlate with an actual clinical endpoint but does not
necessarily have a precise relationship; that is, a biomarker is a
substitute measure for a clinical endpoint.
[0592] As used herein, the terms "treatment," "treat," "treating,"
and the like, mean to include slowing or attenuating the
progression of a disease or disorder. The terms include to
alleviate, ameliorate, or reduce one or more symptoms of a disorder
or condition, even if the disorder or condition is not eliminated
or if the progression is not slowed.
[0593] As used herein "cure diabetes" means that a patient, using
tirzepatide for the treatment of diabetes reaches their glycemic
control treatment goal. The tirzepatide treatment to cure diabetes
can prevent, reduce the severity of, or induce remission of
diabetes in such patient. In an embodiment, tirzepatide treatment
slows the progression of diabetes in a patient in need of such
treatment. In an embodiment, a patient using tirzepatide for
treatment of diabetes, reaches their glycemic control treatment
goal, and requires no concomitant diabetes medicine to maintain the
glycemic control goal. In an embodiment, a patient using
tirzepatide in the treatment of diabetes reaches at least their
glycemic control treatment goal, and the treatment goal is
maintained with cessation of treatment using tirzepatide and all
other diabetes medication. In an embodiment, a patient using
tirzepatide in the treatment of diabetes reaches at least their
glycemic control treatment goal, and the treatment goal is
maintained for at least a about a month with cessation of treatment
using tirzepatide and all other diabetes medications. In an
embodiment, a patient using tirzepatide in the treatment of
diabetes reaches at least their glycemic control treatment goal,
and the treatment goal is maintained for at least about six months
with cessation of treatment using tirzepatide and all other
diabetes medications. In an embodiment the patient is unable to
reach their glycemic goals prior to tirzepatide treatment. In an
embodiment, the patient has failed to reach their glycemic goal
using oral diabetes medication. In an embodiment, the patient has
failed to reach their glycemic goal using metformin treatment. In
an embodiment, the patient glycemic goal is less than about 5.9%
HbA1c.
[0594] As used herein "glycemic control" refers to the maintenance
or reduction of a patient's HbA1c levels; "improving" glycemic
control refers to reductions in HbA1c.
[0595] As used herein "weight management" refers to the management
of obesity in an individual; "improving" weight management refers
to a reduction in body weight.
[0596] As used herein "HbA1c" refers to glycated hemoglobin levels,
which develop when hemoglobin joins with glucose in the blood.
HbA1c levels are a commonly used measure of glycemic control in
patients with diabetes, with decreased HbA1c levels generally
indicating improved glycemic control. In the context of the methods
of the present invention, the methods of the present invention
result in a decrease in HbA1c. In certain embodiments, the decrease
in HbA1c is decreased relative to the HbA1c levels resulting from
treatment with a lower dose of tirzepatide.
[0597] As used herein "patient" or "patients" refers to a mammal in
need of treatment for a condition or disorder. In an embodiment,
the patient is a human with a disease or condition that would
benefit from treatment with tirzepatide.
[0598] The term "LOCF" or last observation carried forward are
recognized by the skilled statistician as a statistical analysis
method that imputes missing data. The term "ITT" or intention to
treat are recognized by the skilled statistician as the intention
to treat analysis method wherein participants are analyzed
according to the group they were originally assigned.
Preparation #1--Tirzepatide Composition containing NaCl
[0599] The composition is prepared substantially as described
herein. The compositions containing 5, 10, 15, 20, 15, and 30 mg/mL
of tirzepatide each contain the ingredients set forth in Table 1.
Acid or base is optionally added to attain the desired pH range.
Water is added quantum satis (q.s.) to one milliliter total final
volume.
TABLE-US-00001 TABLE 1 Formulation of tirzepatide, Phosphate, and
NaCl Ingredient Concentration (mg/mL) Tirzepatide 5, 10, 15, 20,
25, and 30 dibasic sodium phosphate* 1.34 NaCl 8.2 *5 mM phosphate
buffer is used
Preparation #2--Tirzepatide Composition Containing Propylene
Glycol
[0600] The composition is prepared substantially as described
herein. The compositions providing 5, 10, 15, 20, 15, and 30 mg/mL
compositions of tirzepatide each contain the ingredients set forth
in Table 2. Acid or base is optionally added to attain the desired
pH range. Water is added quantum satis to one milliliter total
final volume.
TABLE-US-00002 TABLE 2 Formulation of tirzepatide, Phosphate, and
Propylene Glycol Ingredient Concentration (mg/mL) Tirzepatide 5,
10, 15, 20, 25, and 30 dibasic sodium phosphate* 1.34 Propylene
glycol 15 *5 mM phosphate buffer is used
Clinical Study (NCT03131687) Supporting Maintenance Dose
Embodiments
[0601] A 6-month (26-week) Phase 2 double-blind clinical study is
designed to evaluate the safety, efficacy, and PK/PD of 4 dose
levels (1 mg, 5 mg, 10 mg and 15 mg respectively) of tirzepatide
once weekly by subcutaneous injection compared with dulaglutide 1.5
mg. once weekly (QW) and placebo QW in patients with T2DM who have
inadequate glycemic control with diet and exercise with or without
a stable dose of metformin. Tirzepatide dose is up-titrated to the
maintenance dose using the following weekly dose increments:
TABLE-US-00003 Tirzepatide dose: Weekly Tirzepatide Dose
Increments: 1 mg (LY 1 mg) Week 0-26: 1 mg QW 5 mg (LY 5 mg) Week
0-26: 5 mg QW 10 mg (LY10 mg) Week 0: 5 mg Week 1: 5 mg Week 2-26:
10 mg 15 mg (LY15 mg) Week 0: 5 mg Week 1: 5 mg Week 2: 10 mg Week
3: 10 mg Week 4: 10 mg Week 5: 10 mg Week 6-26: 15 mg
[0602] The study also has a 4-week follow up period. In addition to
safety and efficacy for treating T2DM, efficacy endpoints include
the effect of tirzepatide on HbA1c, FBG, body weight, lipids, and
waist circumference compared with placebo and with dulaglutide 1.5
mg. The study also evaluates the effect of tirzepatide on GI
tolerability, hypoglycemia, hypersensitivity reactions, and
pancreatic safety, as well as the development of treatment-emergent
anti-drug antibodies. Model-based dose response analyses are
performed to predict potential for significant HbA1c lowering and
weight loss in longer studies.
Statistical Analyses:
Efficacy:
[0603] The primary efficacy outcome of HbA1c change from baseline
to the 26-week endpoint is analyzed using a Bayesian dose-response
model. Analyses are performed on the intention to treat population
(mITT) analysis set. Supportive analysis of the primary efficacy
outcome for the mITT dataset are the model for post-baseline
measures (MMRM) with body mass index (BMI) (<30 kg/m.sup.2,
.gtoreq.30 kg/m.sup.2), metformin use, treatment, visit, and
treatment-by-visit interaction as fixed effects, baseline HbA1c as
a covariate, and patient as a random effect.
[0604] The mean weight change from baseline at 12 and 26 weeks,
along with the mean change from baseline of HbA1c at 12 weeks, is
analyzed using similar dose-response models as the primary
analyses. The percentages of patients with .gtoreq.5% or
.gtoreq.10% body weight loss, reaching the HbA1c target of
.ltoreq.6.5% or .ltoreq.7.0% at 26 weeks, or requiring rescue
therapy are analyzed using logistic regression with fixed effects
of treatment and strata, and baseline as a covariate. The changes
from baseline in FBG (fasting blood glucose), SMBG (self-monitored
blood glucose) levels, waist circumference, and mean percentage
change in lipids from baseline to 12 and 26 weeks are analyzed
using a similar MMRM to the one used for the primary analyses.
[0605] Table Abbreviations: Dula 1.5 mg=dulaglutide 1.5 mg once
weekly; LY means tirzepatide, and LY 1 mg=tirzepatide 1 mg once
weekly; LY 5 mg=5 mg once weekly; LY 10 mg=escalation dose group
tirzepatide once weekly with highest dose of 10 mg; LY 15
mg=escalation dose group of tirzepatide once weekly with highest
dose 15 mg; LOCF=last observation-carried-forward; N=number of
patients; pbo=placebo; Week 26=mITT on-treatment data at Week 26
excluding data after study drug discontinuation or rescue drug
initiation; mITT=modified intent-to-treat; SD=standard deviation.
For Table 4, n=number of patients in the population with baseline
and post-baseline value at the specified time point. For Table 6,
LY10 mg=escalation dose group tirzepatide, once weekly with highest
dose of 10 mg; escalation dose: (5 mg weeks 0 and 1), LY15
mg=escalation dose group tirzepatide, once weekly with highest dose
of 15 mg escalation dose: (5 mg weeks 0 and 1; 10 mg weeks 2 to 5);
N=number of patients in specified group, m=number of patients who
experienced new event during interval, FolUp=follow up, T/Wk=Time
range, (week) and %=means percent patients spending at least some
time in treatment group who experienced new event during interval.
For Table 7, n is the number of patients with events meeting the
criteria; N is number of patients in the population; % is percent
of patients in treatment group experiencing the event.
TABLE-US-00004 TABLE 3 HbA1c Data % of Patients % of Patients
Reaching Reaching HbA1c HbA1c Target Target <6% <5.7% (odds
(odds ratio p-value ratio vs. p-value Endpoint vs. placebo) (vs.
pbo) placebo) (vs. pbo) Placebo LOCF 2.0% (--) -- 2.0% (--) -- Week
26 (N = 51) mITT 2.4% (--) -- 2.4% (--) -- Week 26(N = 41) LY 5 mg
LOCF 25.5% (11.8) p = 0.005 3.6% (1.6) p = 0.651 Week 26 (N = 55)
mITT 23.4% (10.5) p = 0.010 4.3% (1.7) p = 0.635 Week 26 (N = 48)
LY 10 mg LOCF 46.0% (28.7) p < 0.001 18.0% (7.8) p = 0.022 Week
26 (N = 51) mITT 51.2% (34.5) p < 0.001 20.9% (7.9) p = 0.025
Week 26 (N = 44) LY 15 mg LOCF 37.7% (22.0) p < 0.001 30.2%
(14.4) p = 0.002 Week 26 (N = 53) mITT 54.3% (48.7) p < 0.001
42.9% (26.6) p < 0.001 Week 26 (N = 35) Dula LOCF 11.1% (4.5) p
= 0.107 1.9% (1.0) p = 0.969 1.5 mg Week 26 (N = 54) mITT 12.8%
(4.5) p = 0.116 2.1% (0.89) p = 0.922 Week 26 (N = 47)
[0606] Data in Table 3 support that 5 mg, 10 mg, and 15 mg doses of
tirzepatide significantly decrease HbA1c from baseline and are
significantly different from placebo. The artisan will appreciate
that HbA1c values of less than 5.7% are consistent with levels
observed in a patient without diabetes. The tirzepatide dose groups
are also significantly different from dulaglutide 1.5 mg.
[0607] The percentage of patients reaching HbA1c treatment goals in
Table 3 show that more patients in the tirzepatide 15-mg group who
stay on study drug are able to reach a treatment goal of
HbA1c.ltoreq.5.7% than any other treatment group.
TABLE-US-00005 TABLE 4 Mean Fasting Glucose Value Mean glucose Week
26/ value Mean change Treatment N (mg/dl) SD from baseline SD
Placebo 40 171.1 46.59 16.7 31.35 LY1 mg 44 154.9 49.36 -6.2 55.25
LY5 mg 48 126.5 33.11 -46.7 48.32 LY10 mg 44 104.8 18.65 -66.9
49.06 LY15 mg 35 110.3 32.13 -56.8 67.29 Dula 1.5 mg 46 140.5 52.69
-34.9 68.35
[0608] As expected from observed changes in HbA1c, the tirzepatide
5 mg, 10 mg, and 15 mg doses significantly decrease fasting serum
glucose compared with placebo and dulaglutide 1.5 mg as shown in
Table 4.
TABLE-US-00006 TABLE 5 Weight Loss % of Patients Achieving Weight %
of Patients Achieving loss .gtoreq.10% (odds p-value Weight loss
.gtoreq.15% Treatment ratio vs. placebo (vs. pbo) (odds ratio vs.
placebo Placebo 0 (--) -- -- 0 (--) -- 0 LY 1 mg LOCF 5.8% (7.1) p
= 0.193 -- 6.8% (6.7) p = 0.218 0 LY 5 mg LOCF 16.4% (20.8) p =
0.036 -- 16.7% (17.2) p = 0.056 6.3% LY 10 mg LOCF 39.2% (67.6) p =
0.003 -- 45.5% (71.7) p = 0.004 25.0% LY 15 mg LOCF 37.7% (66.2) p
= 0.003 -- 54.3% (109.2) p = 0.001 34.3% Dula 1.5 mg LOCF 9.3%
(11.7) p = 0.095 -- 10.6% (10.4) p = 0.121 2.1%
[0609] Table 5 summarizes the proportion of patients who attained a
weight loss target of .gtoreq.5%, .gtoreq.10%, and .gtoreq.15% at
Week 26. The 5 mg, 10 mg, and 15 mg doses of tirzepatide
significantly decrease body weight from baseline and are
significantly different from placebo. The tirzepatide 5 mg, 10 mg,
and 15 mg groups are also significantly different from dulaglutide
1.5 mg
[0610] As shown by Table 5 summarizing a clinical study, a larger
percentage of patients in the tirzepatide 15 mg group were able to
reach a mean body weight reduction of over 15%.
TABLE-US-00007 TABLE 6 Nausea Vomiting and Diarrhea T/ Placebo LY10
mg LY15 mg Dula 1.5 mg Wk N = 51 N = 51 N = 53 N = 54 0 m = 0; 0% m
= 9; 20% m = 17; 32.1% m = 12; 22.2% 1 m = 1; 2% m = 2; 3.9% m =
10; 18.9% m = 2; 3.7% 2 m = 0; 0% m = 2; 3.9% m = 3; 5.8% m = 0;
0.0% 3 m = 0; 0% m = 1; 2.0% m = 6; 11.4% m = 2; 3.8% 4 m = 0; 0% m
= 3; 6.0% m = 3; 5.9% m = 1; 1.9% 5 m = 0; 0% m = 2; 4.0% m = 1;
2.0% m = 0; 0.0% 6 m = 0; 0% m = 1; 2.0% m = 2; 3.9% m = 0; 0.0% 7
m = 1; 2% m = 2; 4.1% m = 3; 5.9% m = 1; 1.9% 8 m = 0; 0% m = 1;
2.0% m = 2; 4.0% m = 0; 0.0% 9 m = 0; 0% m = 2; 4.1% m = 0; 0.0% m
= 1; 1.9% 10 m = 0; 0% m = 0; 0% m = 0; 0.0% m = 0; 0.0% 11 m = 0;
0% m = 0; 0% m = 1; 2.0% m = 0; 0.0% 12 m = 0; 0% m = 1; 2.0% m =
1; 2.1% m = 1; 2.0% >12 < 16 m = 1; 2% m = 1; 2.0% m = 1;
2.1% m = 2; 3.9% >16 .ltoreq. 20 m = 0; 0% m = 1; 2.1% m = 1;
2.1% m = 1; 2.0% >20 m = 1; 2.1% m = 1; 2.1% m = 1; 2.1% m = 4;
7.8% Fol m = 0; 0% m = 1; 2.1% m = 0; 0.0% m = 3; 5.9% Up
[0611] Table 6 illustrates the advantageous effect on
gastrointestinal adverse event incidence using the methods
herein.
TABLE-US-00008 TABLE 7 Decrease Appetite Placebo LY1 mg LY5 mg LY10
mg LY15 mg Dula 1.5 mg Event N = 51 N = 52 N = 55 N = 51 N = 53 N =
54 Decrease Appetite n = 1; n = 2; n = 10; n = 13; n = 10; n = 3;
(reported) 2.0% 3.8% 18.2% 25.5% 18.9% 5.6%
[0612] Decrease in appetite is a centrally mediated effect. The
data presented in Table 7 are reported from a clinical trial,
suggesting that tirzepatide has some centrally mediated effects.
The centrally mediated activity of tirzepatide may provide
additional treatment options for patients seeking a treatment to
provide centrally mediated GIP/GLP1 agonist activity.
[0613] In NCT03131687, the 15 mg dose was associated with higher GI
AEs and higher frequency of patients discontinuing study treatment
early after relatively short escalation. A 15 mg dose with a more
acceptable tolerability profile is desired. Data from NCT03131687,
support 15 mg dose as the highest clinically relevant maintenance
dose as contemplated by the present invention. Escalation schemes,
as claimed herein were investigated to facilitate an acceptably
tolerable 15 mg maintenance dosage. See Clinical Study
(NCT03311724) immediately below.
Clinical Study (NCT03311724) Supporting 2.5 Escalation
Increments
[0614] This is a 12-week treatment with a 1 week screening (Visit
1) followed by a 1 week lead-in (Visit 2), then 12 weeks of
treatment (Visits 3-10, including telephone visits), then followed
by 4-week safety follow-up. It is a Phase 2 study designed to
examine the efficacy and tolerability of subcutaneously once-weekly
tirzepatide compared with placebo in patients with type 2 diabetes
who have inadequate glycemic control with diet and exercise alone
or with a stable dose of metformin. The study was designed per
below and conducted to refine the escalation scheme.
TABLE-US-00009 Tirzepatide dose Group: Weekly Tirzepatide Dose
Increments: Placebo Week 1-12 Group 1 Weeks 1-2: 2.5 mg Weeks 3-4:
5 mg Weeks 5-8: 10 mg Weeks 9-12: 15 mg Group 2 Weeks 1-4: 2.5 mg
Weeks 5-8: 7.5 mg Weeks 9-12: 15 mg Group 3 Weeks 1-4: 4 mg Weeks:
5-8: 8 mg Weeks 9-12: 12 mg
TABLE-US-00010 TABLE 8 HbA1c Data at Week 12 - mITT Population with
On Treatment Dataset % of Patients % of Patients Reaching Reaching
HbA1c HbA1c Target Target <7% <5.7% (odds (odds ratio p-value
ratio vs. p-value Endpoint vs. placebo) (vs. pbo) placebo) (vs.
pbo) Placebo LOCF 12.5 (--) -- 0 (--) -- Week 12 (N = 24) Week 12
10.0 (--) -- 0 (--) -- (N = 20) LY 12 mg LOCF 71.4 (16.1) p <
0.001 3.6 (2.8) p = 0.509 Group 3 Week 12 (N = 28) Week 12 74.1
(56.5) p < 0.001 3.7 (2.5) p = 0.568 (N = 27) LY 15 mg- LOCF
78.6 (25.1) p < 0.001 3.6 (2.9) p = 0.494 Group 1 Week 12 (N =
28) Week 12 87.0 (183.5) p < 0.001 4.3 (3.1) p = 0.482 (N = 23)
LY 15 mg- LOCF 85.2 (37.9) p < 0.001 7.4 (5.0) p = 0.270 Group 2
Week 12 (N = 27) Week 12 84.6 (157.5) p < 0.001 7.7 (4.6) p =
0.321 (N = 26) LOCF = last-observation-carried-forward; LY =
tirzepatide; mITT = modified intent-to-treat; N = number of
patietns; pbo = placebo; Week 12: mITT on-treatment at Week 12,
excluding data after study drug discontinuation or rescue drug
initiation; LOCF Week 12: mITT on-treatment, excluding data after
study drug discontinuation or rescue drug inhibition,
last-observation-carried-forward to Week 12.
[0615] As shown by Table 8, after 12 weeks of treatment, including
an 8-week escalation period, placebo-adjusted changes from baseline
in HbA1c with 12-mg and 15-mg tirzepatide doses were statistically
significant and clinically relevant.
TABLE-US-00011 TABLE 9 Weight Loss Data at Week 12 - mITT
Population with On Treatment Dataset % of Patients % of Patients
Achieving Achieving Weight loss Weight loss .gtoreq.5% (odds
.gtoreq.10% ratio vs. p-value (odds ratio vs. p-value Endpoint
placebo (vs. pbo) placebo (vs. pbo) Placebo LOCF 4.3 (--) -- 0 (--)
-- Week 12 (N = 23) Week 12 5.0 (--) -- 0 (--) -- (N = 20) LY 12 mg
LOCF 63.0 (22.7) p < 0.001 18.5 (10.4) p = 0.101 Group 3 Week 12
(N = 27) Week 12 63.0 (20.7) p = 0.001 18.5 (9.3) p = 0.129 (N =
27) LY 15 mg- LOCF 59.3 (20.5) p = 0.001 14.8 (8.0) p = 0.150 Group
1 Week 12 (N = 27) Week 12 56.5 (17.1) p = 0.003 13.0 (6.2) p =
0.225 (N = 23) LY 15 mg- LOCF 55.6 (17.6) p = 0.002 18.5 (10.6) p =
0.099 Group 2 Week 12 (N = 27) Week 12 57.7 (17.4) p = 0.003 19.2
(9.7) p = 0.121 (N = 26) LOCF = last-observation-carried-forward;
LY = tirzepatide; mITT = modified intent-to-treat; N = number of
patietns; pbo = placebo; Week 12: mITT on-treatment at Week 12,
excluding data after study drug discontinuation or rescue drug
initiation; LOCF Week 12: mITT on-treatment, excluding data after
study drug discontinuation or rescue drug inhibition,
last-observation-carried-forward to Week 12.
[0616] As shown by Table 9, both doses tirzepatide doses had
significant reductions in body weight compared with placebo at 12
weeks.
TABLE-US-00012 TABLE 10 Nausea Vomiting and Diarrhea LY12 mg LY15
mg- T/ Placebo Group 3 LY15 mg-Group 1 Group 2 Wk N = 26 N = 29 N =
28 N = 28 0 m = 3; M = 26 m = 9; M = 29 m = 6; M = 28 m = 4; M = 28
1 m = 1; M = 26 m = 5; M = 29 m = 3; M = 28 m = 4; M = 28 2 m = 0;
M = 25 m = 1; M = 29 m = 2; M = 28 m = 2; M = 28 3 m = 0; M = 25 m
= 3; M = 29 m = 1; M = 27 m = 3; M = 28 4 m = 0; M = 25 m = 3; M =
29 m = 5; M = 27 m = 6; M = 28 5 m = 0; M = 24 m = 0; M = 29 m = 6;
M = 27 m = 2; M = 28 6 m = 0; M = 24 m = 2; M = 29 m = 2; M = 27 m
= 3; M = 28 7 m = 0; M = 24 m = 1; M = 29 m = 0; M = 27 m = 2; M =
27 8 m = 1; M = 24 m = 4; M = 29 m = 4; M = 27 m = 5; M = 27 9 m =
0; M = 24 m = 1; M = 29 m = 0; M = 27 m = 2; M = 27 10 m = 0; M =
24 m = 1; M = 29 m = 3; M = 27 m = 0; M = 27 11 m = 0; M = 24 m =
0; M = 29 m = 2; M = 27 m = 3; M = 27 12 m = 0; M = 23 m = 1; M =
29 m = 0; M = 27 m = 0; M = 27 Follow-up m = 0; M = 23 m = 1; M =
29 m = 0; M = 27 m = 0; M = 27 Overall m = 3; M = 26 m = 14; m =
16; M = 28 m = 13; M = 28 M = 26 LY 12 mg Group 3, above =
escalation dose group of tirzepatide once weekly with sequence of 4
mg .times. 4, 8 mg .times. 4, 12 mg .times. 4 LY 15 mg-Grou 1,
above = escalation dose group of tirzepatide once weekly with
sequenc of 2.5 mg .times. 2, 5 mg .times. 2, 10 mg .times. 4, 15 mg
.times. 4 LY 15 mg-Group 2, above = escalation dose group of
tirzepatide once weekly with sequence of 2.5 mg .times. 4, 7.5 mg
.times. 4, 15 mg .times. 4 M = number of patients who had at least
some time in interval m = number of patients who experienced new
event during interval where newly occurred event means that a
patient has a new onset of an event during that period N = numer of
patients in specified treatment group
[0617] As shown by Table 10, the most common adverse events were
gastrointestinal events, including nausea, vomiting and diarrhea.
Most of these vents were mild to moderate. No patient discontinued
the study due to gastrointestinal tolerability adverse events or
any other adverse vents.
[0618] Based on these data above from NCT03311724 an escalation
scheme using 2.5 mg dose increments per 4 weeks is further
supported.
Biomarkers
[0619] Clinically relevant biomarkers are measured in clinical
studies to further support the use of tirzepatide for treating
chronic kidney disease. In study NCT03131687, no decrease in eGFR
was observed at any dosage. Clinical study laboratory measurements
support the use of tirzepatide in the treatment of chronic kidney
disease. Clinically relevant biomarkers are measured to assess and
support the use of tirzepatide in the treatment of atherosclerosis.
Clinically relevant triglyceride levels decrease in all tirzepatide
treatment groups. Clinical observations support that tirezepatide
can be beneficial for use in the treatment of atherosclerosis.
[0620] Biomarkers predictive of NAFLD are observed during clinical
studies to demonstrate the beneficial effect of tirzepatide in the
treatment of NAFLD. Biomarkers predictive of NASH are observed
during clinical studies to demonstrate the beneficial effect of
tirzepatide in the treatment of NAFLD. HbA1c levels in tirzepatide
treated patients reaching their glycemic control goals, and ceasing
the use of diabetes medications, are measured during follow up to
validate a diabetes cure in such patients.
EXAMPLE 1
Clinical Dosing Regimen
[0621] A clinical trial studying the three maintenance doses of the
present invention (5.0 mg, 10.0 mg and 15.0 mg) in the dosing
regimens of the present invention is conducted as follows.
[0622] The starting dose of tirzepatide is 2.5 mg once weekly for 4
weeks, followed by an increase to 5 mg once weekly, for the
duration of the study low-dose arm.
[0623] For the 10-mg arm, the starting dose of tirzepatide is 2.5
mg once weekly for 4 weeks, then the dose is increased by 2.5 mg
every 4 weeks (5 mg once weekly for 4 weeks then 7.5 once weekly
for four weeks) until the 10-mg dose is reached and maintained for
the duration of the study.
[0624] For the 15-mg arm, the starting dose of tirzepatide will be
2.5 mg once weekly for 4 weeks, then the dose will be increased by
2.5 mg every 4 weeks (5 mg once weekly for four weeks then 7.5 mg
once weekly for four weeks then 10 mg once weekly for four weeks
then 12.5 mg once weekly for four weeks) until the 15-mg
tirzepatide dose is reached and maintained for the duration of the
study. For patients who cannot tolerate the 15 mg dose, the
maintenance dose may be decreased to 10 mg.
Sequences
SEQ ID NO:1
Tirzepatide
[0625] YX.sub.1EGTFTSDYSIX.sub.2LDKIAQKAFVQWLIAGGPSSGAPPPS
[0626] wherein X.sub.1 is Aib; X.sub.2 is Aib; K at position 20 is
chemically modified through conjugation to the epsilon-amino group
of the K side-chain with
(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl).sub.2-(.gamma.Glu).sub.1-CO--(CH.s-
ub.2).sub.18--CO.sub.2H; and the C-terminal amino acid is amidated
as a C-terminal primary amide
Sequence CWU 1
1
1139PRTArtificial SequenceSynthetic
ConstructMISC_FEATURE(2)..(2)Xaa at position 2 is nonnaturally
occurring amino acid 2-Aminoisobutyric
AcidMISC_FEATURE(13)..(13)Xaa at position 13 is nonnaturally
occurring amino acid 2-Aminoisobutyric AcidMOD_RES(20)..(20)Lys at
position 20 is chemically modified through conjugation to the
epsilon-amino group of the K side-chain with
(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-
(gamma-Glu)1-CO-(CH2)18-CO2HMOD_RES(39)..(39)Ser at position 39 is
amidated as a C-terminal primary amide 1Tyr Xaa Glu Gly Thr Phe Thr
Ser Asp Tyr Ser Ile Xaa Leu Asp Lys1 5 10 15Ile Ala Gln Lys Ala Phe
Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 20 25 30Ser Gly Ala Pro Pro
Pro Ser 35
* * * * *