Combined use of metformin and a sodium glucose cotransporter 2 inhibitor (SGLT2I) is a promising treatment strategy for type 2 diabetes. The mechanism by which combination treatment provides better glycemic control than metformin or SGLT2I monotherapy remains elusive.
Therefore, we investigated the physiological mechanism, by which both compounds lower blood glucose concentrations in diabetic mice.
We compared the potential of metformin and the SGLT2I AVE2268 alone or in combination to mitigate hyperglycemia and modulate glucose fluxes in diabetic db/db and Tallyho/JngJ mice.
SGLT2I treatment alone elicited a rapid decline in circulating blood glucose levels, which appeared to induce endogenous glucose production. Supplementation of metformin dampened this counter-response and, therefore, combination therapy more efficiently maintained glycemic control. Finally, combination treatment blunted postprandial glucose excursions and improved HbA1c levels within two weeks.
Taken together, we conclude that co-application of metformin enhances the glucose-lowering actions of SGLT2I by restraining endogenous glucose production what may provide long-term improvement of glycemic control in type 2 diabetic patients.
- Received March 9, 2014.
- Accepted July 23, 2014.
- © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.