Method for treating non-insulin dependent diabetes using thiazolidinediones with glucagonlike peptide-1 and agonists thereof

Abstract

Thiazolidinedione (TZD) and its pharmacologically active derivatives can be used in combination with agonists of glucagon-like peptide-1 (GLP-1), to treat non-insulin dependent diabetes mellitus, optionally with other therapies, by improving glycemic control while minimizing side effects, such as heart hypertrophy and elevated fed-state plasma glucose, which are associated with both TZD and GLP-1 monotherapies. Thus, the co-administration of TZD and GLP-1 helps regulate glucose homeostasis in Type II diabetic patients.

1. A method of treating non-insulin dependent diabetes mellitus comprising co-administering:
 a) an effective dosage of a GLP-1 peptide agonist  GLP-   1  molecule ; and  
 b) an effective dosage of pioglitazone or rosiglitazone.  
 
     
     
       2. The method of  claim 1  wherein an effective dosage of pioglitazone is administered. 
     
     
       3. The method of  claim 1  wherein an effective dosage of rosiglitazone is administered. 
     
     
       4. The method of  claim 1  wherein the GLP-1 agonist is a GLP-1 molecule. 
     
     
       5. The method of claim  4    1  wherein the GLP-1 molecule is an analog of SEQ ID NO:1. 
     
     
       6. The method of  claim 5  wherein the effective dosage of the GLP-1 molecule is in the range of about 5 to about 200 μg per day. 
     
     
       7. The method of  claim 5  wherein the effective dosage of the GLP-1 molecule is in the range of about 20 to about 100 μg per day. 
     
     
       8. The method of  claim 5  wherein the effective dosage of the GLP-1 molecule is in the range of about 30 to about 50 μg per day. 
     
     
       9. The method of  claim 5  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 0.1 mg to about 200 mg per day. 
     
     
       10. The method of  claim 5  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 50 mg to about 200 mg per day. 
     
     
       11. The method of claim  4    1  wherein the GLP-1 molecule is a GLP-1 derivative. 
     
     
       12. The method of  claim 11  wherein the effective dosage of the GLP-1 molecule is in the range of about 5 to about 200 μg per day. 
     
     
       13. The method of  claim 11  wherein the effective dosage of the GLP-1 molecule is in the range of about 20 to about 100 μg per day. 
     
     
       14. The method of  claim 11  wherein the effective dosage of the GLP-1 molecule is in the range of about 30 to about 50 μg per day. 
     
     
       15. The method of  claim 11  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 0.1 mg to about 200 mg per day. 
     
     
       16. The method of  claim 11  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 50 mg to about 200 mg per day. 
     
     
       17. The method of claim  4    1  wherein the GLP-1 molecule comprises Valine, Glycine, Threonine, or Methionine at position 8. 
     
     
       18. The method of  claim 17  wherein the effective dosage of the GLP-1 molecule is in the range of about 5 to about 200 μg per day. 
     
     
       19. The method of  claim 17  wherein the effective dosage of the GLP-1 molecule is in the range of about 20 to about 100 μg per day. 
     
     
       20. The method of  claim 17  wherein the effective dosage of the GLP-1 molecule is in the range of about 30 to about 50 μg per day. 
     
     
       21. The method of  claim 17  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 0.1 mg to about 200 mg per day. 
     
     
       22. The method of  claim 17  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 50 mg to about 200 mg per day. 
     
     
       23. The method of claim  4    1  wherein the effective dosage of the GLP-1 molecule is in the range of about 5 to about 200 μg per day. 
     
     
       24. The method of claim  4    1  wherein the effective dosage of the GLP-1 molecule is in the range of about 20 to about 100 μg per day. 
     
     
       25. The method of claim  4    1  wherein the effective dosage of the GLP-1 molecule is in the range of about 30 to about 50 μg per day. 
     
     
       26. The method of claim  4    1  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 0.1 mg to about 200 mg per day. 
     
     
       27. The method of claim  4    1  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 50 mg to about 200 mg per day. 
     
     
       28. The method of  claim 1  wherein the effective dosage of the GLP-1 agonist is in the range of about 5 to about 200 μg per day. 
     
     
       29. The method of  claim 1  wherein the effective dosage of the GLP-1 agonist is in the range of about 20 to about 100 μg per day. 
     
     
       30. The method of  claim 1  wherein the effective dosage of the GLP-1 agonist is in the range of about 30 to about 50 μg per day. 
     
     
       31. The method of  claim 1  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 0.1 mg to about 200 mg per day. 
     
     
       32. The method of  claim 1  wherein the effective dosage of pioglitazone or rosiglitazone is in the range of about 50 mg to about 200 mg per day. 
     
     
       33. The method of  claim 1  wherein the GLP- 1 agonist  molecule  is administered as a composition comprising a GLP-1 molecule at a concentration of between 10 −12  M and 10 −5  M. 
     
     
       34. The method of  claim 1  wherein the GLP- 1 agonist  molecule  is administered as a controlled release preparation.