Glucokinase activator compositions for the treatment of diabetes
The present invention relates to the use of liver-selective glucokinase activators and a GLP1 analog in restoring insulin sensitivity and treating type II diabetes, including reducing body weight in subjects undergoing type II diabetes treatment.
1. A method of reducing glycosylated hemoglobin HbA1c in a mammal by increasing the mammal's insulin sensitivity comprising:
administering to the mammal a therapeutically effective amount of a liver-selective glucokinase activator in combination with a therapeutically effective amount of a GLP-1 analog or a pharmaceutically acceptable salt thereof,
wherein the mammal has inadequate glycemic control.
2. The method of claim 1 , wherein the mammal is a human.
3. The method of claim 2 , wherein the human has a baseline HbA1c value from about 7.5% to about 15%.
4. The method of claim 2 , wherein the amount of HbA1c is reduced by at least 0.3 percentage points.
5. The method of claim 1 , wherein the liver-selective glucokinase activator is {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the liver-selective glucokinase activator and the GLP-1 analog are administered in discrete dosage forms.
7. The method of claim 6 , wherein the GLP-1 analog is administered by injection and the liver-selective glucokinase activator is administered orally.
8. The method of claim 1 , wherein the liver-selective glucokinase activator and the GLP-1 analog are administered in a single dosage form.
9. The method of claim 1 , wherein the GLP-1 analog is exenatide or a pharmaceutically acceptable salt thereof.
10. A method of reducing glycosylated hemoglobin HbA1c in a human by increasing the human's insulin sensitivity comprising:
administering to the human a therapeutically effective amount of a liver-selective glucokinase activator in combination with a therapeutically effective amount of a GLP-1 analog or a pharmaceutically acceptable salt thereof,
wherein the human has impaired glucose metabolism,
wherein the liver-selective glucokinase activator is {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof.
11. The method of claim 10 , wherein the human has a baseline HbA1c value from about 7.5% to about 15%.
12. The method of claim 10 , wherein the amount of HbA1c is reduced by at least 0.3 percentage points.
13. The method of claim 12 , wherein the amount of HbA1c is reduced by at least 0.4 percentage points.
14. The method of claim 10 , wherein the liver-selective glucokinase activator and the GLP-1 analog are administered in discrete dosage forms.
15. The method of claim 14 , wherein the GLP-1 analog is administered by injection and the liver-selective glucokinase activator is administered orally.
16. The method of claim 10 , wherein the liver-selective glucokinase activator and the GLP-1 analog are administered in a single dosage form.
17. The method of claim 10 , wherein the GLP-1 analog is exenatide or a pharmaceutically acceptable salt thereof.