Metformin: The age-old elixir of life?


Exploring the potential of a common drug in the quest for longevity. Image credit: Markus Spiske, via Unsplash.

Cancer and cardiovascular disease are the two leading causes of death worldwide. Between them, they account for almost half of all deaths for people over 70. As we get older, our cells also “age” as they accumulate damage over time, and it is this process of ageing which means people develop fatal diseases later in life. A method to slow or reverse this ageing would reduce mortality, and it is only in the last decade that a feasible candidate has emerged—metformin.

Despite the relatively recent acknowledgement of metformin’s potential as an anti-ageing remedy, its discovery dates back to the early 20th century when the medicinal herb, Galega officinalis, was shown to lower blood glucose. This plant was then used to develop the drug metformin, first used in the late 1950s for the treatment of type II diabetes. Despite this, it was only in the late 1990s that it was formally approved by the FDA for the treatment of type II diabetes, and it has now become one of the most prescribed medications worldwide.

A 2014 study found that patients with type II diabetes who were taking metformin survived longer on average than non-diabetic patients. Indeed, they found that when compared to diabetic patients taking metformin, the age-adjusted median survival times of non-diabetic patients were up to 15% lower. The patients taking metformin seemed to be living longer.

Despite these promising results, the study used an observational approach meaning that it could only demonstrate correlation, and not causation, between taking metformin and increased lifespan. A more direct interventional approach is instead required to demonstrate causation.

If metformin is proven to have anti-ageing properties, the implications are massive. Metformin costs pennies per pill, permitting indiscriminate access to both rich and poor.

Dr Nir Barzilai, director of the Institute for Ageing Research at the Albert Einstein College of Medicine in New York, has teamed up with other researchers to design an interventional trial called Targeting Aging with Metformin (TAME).

Subject to funding and approval, the TAME trial plans to enrol 3000 people aged 65–79 who will be randomly divided into two groups which take either a metformin or placebo pill, a pill with no active ingredients used to set a benchmark for genuine effect, daily for a period of six years. A carefully devised list of parameters will be used to measure ageing, to definitively assess whether metformin slows down ageing, the incidence of age-related diseases and ultimately death.

In 2019, Barzilai secured a significant $35 million contribution (of a required $50–75 million) towards running TAME from the American Federation for Ageing Research (AFAR). Currently, fundraising for the trails is underway, and, with a potential investment on the cards from the not-for-profit organisation, Hevolution, it is likely that the TAME trial will be started in due course.

If metformin is proven to have anti-ageing properties, the implications are massive. Metformin costs pennies per pill, permitting indiscriminate access to both rich and poor. Its long history of use also provides evidence for its safety. However, the drug still has well-documented side effects and thus metformin should only be taken after consultation with a doctor.

At this stage, there has been conflicting evidence of metformin’s efficacy, and many questions remain unanswered. The effects of metformin in non-diabetics are yet to be determined as well as the required dosage needed for anti-ageing benefits. The TAME trial, which hopes to begin as soon as funding is secured, will shed some light on the true capabilities of the drug and hopefully provide answers to some of these key questions.