Use of metformin in combination with a glucokinase activator and compositions comprising metformin and a glucokinase activator
The present invention provides uses of a glucokinase activator in combination with metformin. Uses include treating type 2 diabetes, lowering blood glucose, improving insulin sensitivity, enhancing phosphorylation of glucose, and improving the therapeutic effectiveness of metformin. The invention also provides pharmaceutical compositions that comprise a GK activator and metformin. The invention also provides a salt formed between metformin and a GK activator.
1. A method of lowering blood glucose in a subject comprising:
administering to the subject {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof in combination with metformin, wherein the metformin is administered in an amount of less than 1000 mg/day.
2. The method of claim 1 , wherein the metformin is administered in an amount between 0.01 mg/day and less than 1000 mg/day.
3. The method of claim 1 , wherein the metformin is administered in an amount between 10 mg/day and 850 mg/day.
4. The method of claim 1 , wherein the metformin is administered in an amount between 10 mg/day and less than 1000 mg/day.
5. The method of claim 1 , wherein {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid is administered in an amount of less than 1000 mg/day.
6. The method of claim 1 , wherein the metformin is 1,1-dimethylbiguanide monohydrochloride.
7. The method of claim 2 , wherein the metformin is 1,1-dimethylbiguanide monohydrochloride.
8. The method of claim 3 , wherein the metformin is 1,1-dimethylbiguanide monohydrochloride.
9. The method of claim 4 , wherein the metformin is 1,1-dimethylbiguanide monohydrochloride.
10. The method of claim 5 , wherein the metformin is 1,1-dimethylbiguanide monohydrochloride.
11. The method of claim 1 , wherein the subject is a human.
12. The method of claim 11 , wherein the subject is suffering from type 2 diabetes.
13. The method of claim 1 , wherein the {1-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof and the metformin are administered in the same dosage form.
14. The method of claim 1 , wherein the {1-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof and the metformin are administered in separate dosage forms.
15. The method of claim 1 , wherein the {1-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof and the metformin are administered simultaneously.
16. The method of claim 1 , wherein the {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid or a pharmaceutically acceptable salt thereof and the metformin are administered in sequence so that a synergistically effective amount of both are simultaneously present in the subject.