“Metformin and Aging: A Review”, 2019-09-13 (; backlinks; similar):
Metformin is sometimes proposed to be an “anti-aging” drug, based on preclinical experiments with lower-order organisms and numerous retrospective data on beneficial health outcomes for type 2 diabetics. Large prospective, placebo-controlled trials are planned, in pilot stage or running, to find a new use (or indication) for an aging population. As one of the metformin trials has “frailty” as its endpoint, similar to a trial with a plant-derived senolytic, the latter class of novel anti-aging drugs is briefly discussed. Concerns exist not only for vitamin B12 and B6 deficiencies, but also about whether there are adverse effects of metformin on individuals who try to remain healthy by maintaining cardiovascular fitness via exercise.
…Conclusions, Recommendations, and Perspectives: The rationale for the ongoing or planned metformin trials is almost exclusively based on observations (associations) of potential benefits in a diabetic (or prediabetic) population. Its efficacy even in an at-risk cohort of aged people has not yet been proven. Metformin is associated with a higher risk of vitamin B12 and vitamin B6 deficiency, which may result in an increased risk of cognitive dysfunction98. Supplementation is strongly recommended to metformin users.
Of greater concern are the results of small trials in which the effects of metformin on metabolic responses to exercise or on cardiorespiratory fitness were tested. In a placebo-controlled, double-blind, crossover trial with healthy young subjects, metformin caused a small but statistically-significant decline in maximal aerobic capacity99. A double-blind, placebo-controlled landmark trial with older adults with one risk factor for T2D investigated the effects of metformin and 12 weeks of aerobic exercise100. Contrary to expectations—namely, that the effects of exercise and the drug would be additive–“metformin attenuated the increase in whole-body insulin sensitivity and abrogated the exercise-mediated increase in skeletal muscle mitochondrial respiration.” The results of the (repurposing) MASTERS trial (NCT02308228; Metformin to Augment Strength Training Effective Response in Seniors)100 will be instructive. MASTERS is testing the hypothesis that older individuals’ long-term treatment with metformin augments the effects of resistance exercise, especially in the “nonresponder” aging population.
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