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Metformin increases endogenous glucose production in non-diabetic individuals and individuals with recent-onset type 2 diabetes – published online 11/04/2019

Figure from Gormsen paper

Lars C. Gormsen, Esben Søndergaard, Nana L. Christensen, Kim Brøsen, Niels Jessen, Søren Nielsen


Although metformin is the endorsed first-line glucose-lowering drug for individuals with type 2 diabetes, the exact mechanisms by which the drug exerts its effects are still debated. Studies in individuals with poorly controlled diabetes have indicated that the main site of action is the liver, through reduced hepatic gluconeogenesis, whereas others have demonstrated that the drug may increase intestinal glucose uptake. In this issue, Gormsen et al ( report that 3 months of metformin treatment lowered blood glucose as expected but, surprisingly, it increased endogenous glucose production. This effect was observed both in individuals with recent-onset type 2 diabetes and age-matched non-diabetic healthy individuals. The authors suggest that the primary glucose-lowering effect of metformin may, thus, be extra-hepatic, at least in healthy individuals and patients with recent-onset diabetes.

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