There have been suggested that metformin, a at best weak calorie restriction mimetic, can suppress some of the beneficial metabolic response to exercise. Metformin is in general a poor choice in comparison to mTOR inhibitors when it comes to animal evidence for an ability to modestly slow the progression of aging. The primary human evidence for metformin to be useful, and why it attracted interest in the first place, comes from a large study of diabetic patients, and the gain in life expectancy was not large. Researchers here provide evidence against any suppression by metformin of beneficial mechanisms resulting from exercise, but I can't say that this does much to make metformin an attractive option. At the end of the day, small effect sizes are just not worth chasing, given the many other lines of research and development that offer greater promise.
Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise with or without metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed.
Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress, and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g. the gut.