The potential of metformin in weight loss

Metformin, as a unique first-line antidiabetic drug, it may also be effective in the treatment of obesity and related metabolic disorders. In meta-analyses and numerous RCTs in obese persons with and without type 2 diabetes mellitus with metformin, a decrease in weight and fat mass (≈ 3 kg), as well as blood lipids and adiponectin was noted. Mechanisms of metformin action for weight loss, dependent and independent of AMP-activated protein kinase (AMPK): enhancement of mitochondrial biogenesis, reduction of fatty acid uptake, due to suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, modulation of the gut microbiota and regulation of a number of other signals – fructose-1.6-biphosphatase 1 (FBP1), protein phosphatase 2 (PP2A), fibroblast growth factor 21 (FG F21), sirtuin 1 (SIRT1), target of rapamycin (mTOR), etc., reduction of lipogenic gene expression, which leads to decrease in energy intake. However, there is conflicting evidence that metformin has little effect on weight loss, energy intake, and body composition – its effect varies depending on gender, age, duration of treatment, does not necessarily persist after treatment is stopped, does not significantly affect body composition. Metformin worldwide and in the Russian Federation has not yet been included in list of medications for the treatment of obesity. Comprehensive, adequately powered studies with longer treatment durations are needed to further evaluate the efficacy and safety of metformin for weight loss and weight gain control.