Acute effect of metformin on intestinal sodium-glucose co-transport / – MET-INTESTIN

Acute effect of metformin on intestinal sodium-glucose co-transport

Metformin is widely used to treat type 2 diabetes but its mechanisms of action remain uncertain. Converging evidences now indicate that this non metabolized agent might primarily act in the gut. Preliminary data obtained by the partners suggest that metformin reduces intestinal glucose absorption by modulating active sodium-glucose cotransport.

The overall objective of this project is to demonstrate this unexpected acute effect of metformin on intestinal sodium-glucose co-transport in preclinical models and its clinical relevance for the treatment of type 2 diabetes. The specific aims are (1) to explore the acute effect of metformin on active sodium-glucose co-transport in cellular models and genetically modified mice; (2) to characterize the acute effect of metformin on intestinal glucose absorption and postprandial metabolic signature in a large animal model, and (3) to assess its clinical relevance on intestinal glucose transport in patients with type 2 diabetes.

The uncovering of a novel mechanism of action of metformin will contribute to the axes 4 and 7 of challenge B4. By promoting a more effective use of this widely used antidiabetic drug, this project will potentially impact millions of patients worldwide.