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US-12616740-B2 - Methods of using a GIP/GLP1 co-agonist for therapy

US12616740B2US 12616740 B2US12616740 B2US 12616740B2US-12616740-B2

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

  • Charles T. BENSON
  • Axel Haupt
  • Melissa Kay THOMAS
  • Shweta URVA

Assignees

  • ELI LILLY AND COMPANY

Dates

Publication Date
20260505
Application Date
20250523

Claims (20)

  1. 1 . A method for treating type 2 diabetes in a patient comprising: administering to the patient tirzepatide in once-weekly doses, the administering comprising: administering a first once-weekly dose of 2.5 mg for four weeks; increasing the once-weekly dose by increments of 2.5 mg to a once weekly maintenance dose of 5, 10, or 15 mg, wherein each increased once weekly dose is administered for at least four weeks; and administering the maintenance dose of 5, 10, or 15 mg once weekly to treat type 2 diabetes in the patient, wherein the patient has type 2 diabetes and the tirzepatide is administered subcutaneously to the patient.
  2. 2 . The method of claim 1 , further comprising administering metformin to the patient.
  3. 3 . The method of claim 1 , wherein the maintenance dose is 5 mg.
  4. 4 . The method of claim 1 , wherein the maintenance dose is 10 mg.
  5. 5 . The method of claim 1 , wherein the maintenance dose is 15 mg.
  6. 6 . A method for treating obesity in a patient comprising; administering to the patient tirzepatide in once-weekly doses, the administering comprising: administering a first once-weekly dose of 2.5 mg for four weeks; increasing the once-weekly dose by increments of 2.5 mg to a once weekly maintenance dose of 5, 10, or 15 mg, wherein each increased once weekly dose is administered for at least four weeks; and administering the maintenance dose of 5, 10, or 15 mg once weekly to treat obesity in the patient, wherein the tirzepatide is administered subcutaneously to the patient.
  7. 7 . The method of claim 6 , further comprising administering metformin to the patient.
  8. 8 . The method of claim 6 , wherein the maintenance dose is 5 mg.
  9. 9 . The method of claim 6 , wherein the maintenance dose is 10 mg.
  10. 10 . The method of claim 6 , wherein the maintenance dose is 15 mg.
  11. 11 . A method for improving glycemic control in a patient with type 2 diabetes, comprising: administering tirzepatide at a dosage of 2.5 mg once weekly for at least four weeks, and increasing the dosage to 5 mg once weekly, wherein tirzepatide is administered by subcutaneous injection.
  12. 12 . The method of claim 11 , further comprising increasing the dosage to 7.5 mg once weekly after at least four weeks at 5 mg once weekly.
  13. 13 . The method of claim 12 , further comprising increasing the dosage to 10 mg once weekly after at least four weeks at 7.5 mg once weekly.
  14. 14 . The method of claim 13 , further comprising increasing the dosage to 12.5 mg once weekly after at least four weeks at 10 mg once weekly.
  15. 15 . The method of claim 14 , further comprising increasing the dosage to 15 mg once weekly after at least four weeks at 12.5 mg once weekly.
  16. 16 . A method for treating obesity in a patient, comprising administering tirzepatide at a dosage of 2.5 mg once weekly for at least four weeks, and increasing the dosage to 5 mg once weekly, wherein tirzepatide is administered by subcutaneous injection.
  17. 17 . The method of claim 16 , further comprising increasing the dosage to 7.5 mg once weekly after at least four weeks at 5 mg once weekly.
  18. 18 . The method of claim 17 , further comprising increasing the dosage to 10 mg once weekly after at least four weeks at 7.5 mg once weekly.
  19. 19 . The method of claim 18 , further comprising increasing the dosage to 12.5 mg once weekly after at least four weeks at 10 mg once weekly.
  20. 20 . The method of claim 19 , further comprising increasing the dosage to 15 mg once weekly after at least four weeks at 12.5 mg once weekly.

Description

This application is a continuation application of U.S. application Ser. No. 17/366,453, which is a divisional application of U.S. application Ser. No. 16/518,513, filed on Jul. 22, 2019, which claims priority to U.S. Provisional Application No. 62/740,619, filed on Oct. 3, 2018, to U.S. Provisional Application No. 62/730,565, filed on Sep. 13, 2018, and to U.S. Provisional Application No. 62/702,061, filed on Jul. 23, 2018. The disclosure of each of the above applications is incorporated herein by reference in its entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING The present application is being filed along with a Sequence Listing in ST.26 XML format. The Sequence Listing is provided as a file titled “X22001C_US.xml” May 14, 2025, and is 198 KB kilobytes in size. The Sequence Listing information in the ST.26 XML format is incorporated herein by reference in its entirety. No new matter is added herewith. 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. 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. 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. 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. 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. The present invention provides novel tirzepatide dosing regimens for use in the aforementioned therapies that include a maintenance dose selected from the group