In September 2024, the scientific journal Cell published a paper suggesting that metformin slows the pace of biological aging in male primates. Metformin is an FDA-approved prescription medication commonly used to treat type 2 diabetes by improving insulin sensitivity and decreasing the amount of glucose produced by the liver. After examining the influence of metformin supplementation on a suite of physiological, imaging, histological, transcriptomic, and RNA sequencing parameters, the paper's authors concluded that metformin exerts geroprotective effects on various tissues.

Matt and Nick spend this episode dissecting the paper, highlighting potential improvements to study design and presentation, and discussing the use of metformin as a longevity drug.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Metformin decelerates aging clock in male monkeys

This paper is the focus of the podcast episode. The authors measured the effects of metformin on a large number of parameters in male monkeys aged between 13 and 16 years, which is equivalent to about 40 to 50 human years. They found that metformin administration slowed aging indicators, including "hallmarks of aging" such as inflammation and cellular senescence, across various tissues.

Can people with type 2 diabetes live longer than people without diabetes? A comparison of all-cause mortality in people initiated with metformin monotherapy or sulfonylurea monotherapy and matched controls without diabetes.

Researchers compared survival rates of patients with type 2 diabetes taking metformin to those taking sulfonylurea as well as to people without diabetes, and found that type 2 diabetics on metformin had longer adjusted survival than both other groups. They suggest that, based on these data, type 2 diabetes patients treated with metformin might have survival at least equivalent to that of non-diabetics.

Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis

In this meta-analysis, authors gathered available research examining mortality and diseases of aging in diabetics taking metformin versus non-diabetics or diabetics undergoing other therapeutic interventions. They found that all-cause mortality among diabetics taking metformin was lower than that of non-diabetics as well as diabetics receiving therapies other than metformin. They also noted that metformin supplementation reduced rates of developing any cancer compared to rates observed in the general population.

Metformin Retards Aging in C. elegans by Altering Microbial Folate and Methionine Metabolism

This paper is one of several suggesting a life- and/or healthspan extension in Caenorhabditis elegans, a nematode worm. The study found that metformin brought about dose-dependent lifespan increase of up to 36 percent in C. elegans. The lifespan-extension effects of metformin disappeared when worms received a high-glucose diet. The authors suggest that microbes such as Escherichia coli influence the effects of metformin on worms, and propose mechanisms by which this interaction might occur.

The Targeting Aging with Metformin (TAME) Trial

The TAME trial is a large-scale investigation of whether metformin delays the onset and development of age-related diseases in humans. Currently, the trial aims to enroll 3,000 men and women aged 65 to 79 years at 14 research institutions across the United States. Raising funding for the trial has been a challenge, in part because metformin is an off-patent drug and thus no particular company stands to benefit financially from the potential discovery that metformin exerts geroprotective effects in humans.