Metformin supports the antidiabetic effect of a sodium glucose cotransporter 2 inhibitor by suppressing endogenous glucose production in diabetic mice

Susanne Neschen, Markus Scheerer, Anett Seelig, Peter Huypens, Jürgen Schultheiss, Moya Wu, Wolfgang Wurst, Birgit Rathkolb, Karsten Suhre, Eckhard Wolf, Johannes Beckers, Martin Hrabé De Angelis

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22 Citations (Scopus)

Abstract

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 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 production. Supplementation of metformin dampened this counterresponse, and therefore, combination therapy more efficiently maintained glycemic control. Finally, combination treatment blunted postprandial glucose excursions and improved HbA1c levels within 2 weeks. We conclude that coapplication of metformin enhances the glucoselowering actions of SGLT2I by restraining endogenous glucose production, which may provide long-term improvement of glycemic control in type 2 diabetic patients.

Original languageEnglish
Pages (from-to)284-290
Number of pages7
JournalDiabetes
Volume64
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Neschen, S., Scheerer, M., Seelig, A., Huypens, P., Schultheiss, J., Wu, M., Wurst, W., Rathkolb, B., Suhre, K., Wolf, E., Beckers, J., & De Angelis, M. H. (2015). Metformin supports the antidiabetic effect of a sodium glucose cotransporter 2 inhibitor by suppressing endogenous glucose production in diabetic mice. Diabetes, 64(1), 284-290. https://doi.org/10.2337/db14-0393