How Metformin Could Potentially Increase Life Longevity

What To Know About Metformin: The Decades-Old Diabetes Drug Fueling Billions in Longevity Research

Photographed by Makie Cruz

A decades-old diabetes drug that costs mere pennies to produce holds the potential to radically shift how we think about the human lifespan. Consistently namechecked by the biggest players in the longevity space, including Dr. David Sinclair and Dr. Mark Hyman, metformin lowers blood sugar while activating the “longevity enzyme.” 

“Metformin has been shown to prevent diabetes, it has been shown to prevent cancer, it has been shown to prevent cognitive decline and Alzheimer’s,” says Nir Barzilai, MD, a professor at the Albert Einstein College of Medicine and one of the leading metformin researchers in the world. “It has been shown to decrease mortality.”

With possible life-lengthening potential, biotech companies and start-ups with billions behind to invest have taken note. Reports suggest that nearly $15 billion was pumped into the longevity space in 2021 and 2022 alone, and many of the big contributors reportedly pop metformin daily. Sam Altman, the high-profile former CEO of Open AI, takes the stuff and recently invested a whopping $180 million of his personal funding in Retro Biosciences, an anti-aging cell regeneration company. Bryan Johnson, the biotech billionaire who’s been reported to spend $2 million per year to have the body of an 18-year-old and invests heavily in longevity, also takes it daily.

“If you would ask me if [metformin] has kicked off or motivated biotech and start-ups—and even some more well-established long-term drug companies—to do more in longevity,” says Evelyne Bischof, the founding vice president of Healthy Longevity Medicine Society, “I would say a big, big, yes.”

Expanding the amount of time that humans can live, however, is only part of the aim, as longevity experts like Peter Attia, MD, author of Outlive, The Science and Art of Longevity, would say. The other component is extending the period of time that they’re living without diseases. Placed in the current landscape wherein American mortality is on the decline and at the youngest it has been in almost two decades—with preventable diseases accounting for a bulk of deaths—metformin emerges as a promising treatment route for doctors to prescribe to their patients, due to its shown wide-ranging improvements on different systems in the body.

While the scientific community is optimistic about metformin, it’s essential to balance this optimism with a cautious approach, which is why many metformin researchers are pushing to have the Targeting Aging with Metformin or TAME study funded to prove its ability to act as a longevity drug. This will allow it to hop from billionaire circles into the lives of those who need it most.

What is metformin?

Metformin was first approved by the Food and Drug Administration in 1994, though earlier formulations have been around as early as the 1920s. An extract of the French lilac, “it would be a nutraceutical, but it’s actually modulated a little bit,” says Barzilai, who says it was shown to prevent flu and malaria. Eventually, the early stage of the drug was studied to be an effective way to lower glucose levels, which led to its eventual adoption for diabetes. And soon after that, researchers noticed that many of the people who took it had younger-functioning hearts, better blood pressure, and improved cognitive function.

The drug is part of a class of antihyperglycemic drugs called “biguanides,” which are intended to decrease the amount of glucose that the liver produces and your body absorbs, but it also activates an enzyme called “AMP-activated protein kinase” or AMPK, which has been coined the “longevity enzyme.” This enzyme boosts cells’ ability to use energy and could potentially contribute to longevity by reducing age-related cellular stress. And it helps with a process called “telomere attrition.” “Telomeres are like aglets at the end of a shoelace—they protect the ends of the linear chromosomes and help prevent instability,” explains VJ Periyakoil, MD, a professor of medicine at Stanford University. As we age, these telomeres or “aglets” get shorter and shorter until they can’t divide anymore, and when this happens, our tissues age. But metformin blunts this process, keeping telomeres intact and well functioning.

In short, the drug acts via multiple different mechanisms to keep your cells and your body from rapidly undergoing aging processes on a cellular level that ultimately lead to decline and death. But it’s important to note that while many hold up metformin’s promise for longevity through various one-off research studies, a recent longitudinal study couldn’t replicate these results, thus calling them into question. Given this, it’s important for clinical trials—like the TAME study—to come to fruition so that we can deeply understand the true promise of metformin for longevity. Or in other words, it’s crucial to remain skeptical until more large-scale, long-term clinical trials validate metformin’s effectiveness in extending the lifespan.

Who is metformin right for?

Metformin has long been beneficial—and is approved—for people with diabetes. Outside of that, it has been doctors who study the drug say that it has a few indications where it’s particularly helpful: Women with PCOS have been helped by the drug, so, too, have folks above 50, but as for the rest of us, it’s a game of consult your doctor and weigh your options.

Barzilai cautions against healthy, young people incorporating it into their repertoires carte blanche. “I don’t think that people who are 20 years old who take metformin are going to have any benefit,” he says. “Metformin is a drug that works well when you have the biology of aging, not otherwise from this perspective.” One reason, explain doctors, is that metformin can impact certain biomarkers, changing growth hormone levels and testosterone levels in men. Some studies have also proven that metformin can inhibit muscle growth (though, importantly, it creates better quality muscle), making it a less-than-optimal choice for people who live active lives.

Is it approved by the FDA to take for longevity?

Right now, metformin taken for any other use than to help regulate blood sugar is considered “off-label use.” But that hasn’t stopped a myriad of DTC start-ups from selling the stuff to customers with the hopes of expanding their lifespans and managing their weight. Brands like Ageless RXHone Health, and Sequence, the newly introduced medication arm of WW (formerly known as Weight Watchers), will prescribe you metformin after consulting with a digital healthcare provider. Because of the Ozempic and Wegovy craze, some people are turning to metformin for potential weight management; however, metformin functions via a different mechanism to lower blood sugar, and experts say it isn’t proven to be an effective weight loss drug. In one study, for example, less than one-third of patients lost five percent of body weight.

While those with money and information can access metformin via these DTC companies who are charging a premium, it is still not widely accessible, given the FDA restrictions, for the populations that could likely benefit most. Costing less than both Tylenol or Advil to produce (by some estimations, a mere five cents per pill), with further research, metformin could be a big player in doctor’s toolkits. “We need an indication to target aging by the FDA,” adds Barzilai. “If we don’t have that, then health care providers can say, well, if there’s no FDA indication, we’re not paying for the drug, and if the FDA says we’re not paying for the drug, the pharmaceutical companies that can develop better drugs, and combination drugs, will not come to our field.”

In other words, it stays in the billionaire’s arena, off-label through DTC companies, and out of public health officials’ hands. This means private, venture-backed companies can churn on cell regeneration, but the work stays unfunded in the public health sector. FDA approval would make the drug accessible to the common person and put more government funds behind the longevity drug.

How does this shift the longevity landscape?

For starters, the metformin renaissance makes us rethink cheap, old drugs that aren’t necessarily moneymakers for other uses. “It’s very important for the future to know that metformin is a representative of a very cheap drug, and we should not dismiss something just by the fact that it’s old and cheap,” says Dr. Bischof. “It doesn’t always have to be new and super expensive to make hype and be effective.”

Barzilai says that there are three main ways that longevity researchers are approaching their field. The first is getting approval on existing drugs that can help with longevity outcomes; second, he says is identifying drugs that can improve health for older populations; and third, identifying drugs to keep us young, which he suspects will make their arrival in 50 years. While biotech companies are tight-lipped on their research into reprogramming cells, many in the industry posit that the future of aging won’t look all that different from traditional medicine.

After all, in the 1800s, lifespans were only roughly 40 years. That they’ve close to doubled over the course of two centuries is due fully to medical advancements—all of which prevent disease and stave off death—making all drugs, in their own right, in the business of longevity. Given the current rate of medical advancements, it won’t take two centuries for scientists to help us double lifespans again, especially with the cash influx from billionaires who’ve had immortality dangled in front of their eyes. 

Today, metformin, tomorrow (and the next day and next day), life everlasting.

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