The many lives of metformin


By John DiTraglia



Metformin a cheap and effective drug that is highly recommended for type 2 diabetes. It has also used for polycystic ovary disease has been recommended as a weight loss drug and has been widely used (off-label) as a secret weapon for extending healthspan. But metformin has a complicated history and it’s mechanisms of action are still not totally understood.

Metformin is a member of the biguanidine class of drugs and was originally derived from the French lilac bush. Other members of this class were found early on to be too poisonous because they caused lactic acidosis. Metformin was originally withdrawn from the market due to its relatives. But then it was found to be safe although in very high overdoses it can also cause lactic acidosis. Since it’s reintroduction it has become the most widely prescribed drug for type 2 diabetes because it does not cause weight gain or dangerous hypoglycemia like the other traditional antidiabetes medicatons – insulin, sulfanureas and the glitazones. Now there are reports as I have written in a previous fat science article (2) that metformin might undo some of the benefit of exercise. Since exercise is such a God send for health and longevity this finding may undermine the use of metformin to slow aging.

A brand new study examining this issue was recently reported (3) and has already stirred up commentary in the New York Times. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET). In a double‐blinded fashion, a group of 62 year old participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24‐hr ambulant mean glucose, and glycemic variability. All the usual wonderful things that exercise does. However, metformin decreased to some extent the improvement in whole‐body insulin sensitivity and oxygen uptake after AET. The effects of metformin seem to be because of its actions in the mitochondria of muscle cells. Remember the mighty mitochondria are the power source in your cells. But the effects of metformin were highly variable. These authors concluded that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.

OK that’s aerobic exercise. What about the other kind of exercise that builds muscles that is also good for those of us who don’t want to get old. Well, a different group that has published an even more recent report in the same journal, Aging Cell, is glad you asked. (4) These guys found basically the same worry about metformin, that it negatively impacts the muscle building response to resistance training in a study group of 93 healthy older individuals when compared to placebo.

So confusion worse confounded. If you have type 2 diabetes then the benefits of metformin almost certainly outweigh these issues. If you don’t have type 2 diabetes and can’t or won’t exercise then metformin might make you live longer and better. If you don’t have type 2 diabetes and do exercise then taking metformin might not be beneficial to you. But remember the effects of metformin were highly variable and maybe for some people it would be of added benefit or maybe just taking it while you sleep and aren’t exercising would be good.

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By John DiTraglia

John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- jditrag@zoomnet.net or phone (740) 354-6605.

1. Flory J, Lipska K. Metformin in 2019 JAMA 2019;321(19):1926.

2. DiTraglia J. Metformin can undo exercise. Portsmouth Daily Times. February 16, 2014

3. Konopka AR, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. 2019 Feb; 18(1): e12880. Published online 2018 Dec 11. doi: 10.1111/acel.12880

4. Walton RG et al. Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double‐blind, placebo‐controlled, multicenter trial: The MASTERS trial. Aging Cell; 26 September 2019 https://doi.org/10.1111/acel.13039

John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- jditrag@zoomnet.net or phone (740) 354-6605.

1. Flory J, Lipska K. Metformin in 2019 JAMA 2019;321(19):1926.

2. DiTraglia J. Metformin can undo exercise. Portsmouth Daily Times. February 16, 2014

3. Konopka AR, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. 2019 Feb; 18(1): e12880. Published online 2018 Dec 11. doi: 10.1111/acel.12880

4. Walton RG et al. Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double‐blind, placebo‐controlled, multicenter trial: The MASTERS trial. Aging Cell; 26 September 2019 https://doi.org/10.1111/acel.13039