Inhibitor by Suppressing

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 concentra-tions in diabetic mice. We compared the potential of metformin and the SGLT2I AVE2268 alone or in combina-tion tomitigate hyperglycemia andmodulate glucose fluxes in db/db and diabetic Tallyho/JngJ mice. SGLT2I treatment alone elicited a rapid decline in circulating blood glucose levels, which appeared to induce endogenous glucose pro-duction. Supplementation of metformin dampened this counterresponse, and therefore, combination therapy mor