People are taking a 20-cent 'wonder drug' to slow aging and lose weight. Some doctors say it's promising.
Metformin, an inexpensive, decades-old pill, helps treat diabetes and aids weight loss.
Some research suggests it may also help blunt the effects of aging, preventing cancers and dementia.
New studies are coming, but one researcher says older people should ask doctors about taking it now.
When Dana Bowling started taking metformin in 2010, she wasn't necessarily interested in losing any weight. The 28-year-old had polycystic ovary syndrome, which was preventing her from ovulating, and she wanted to start a family.
Her doctor prescribed metformin, a decades-old diabetes drug that costs about 10 to 20 cents a pill, to trigger her cycle. Within months, Bowling had lost 10 pounds – a significant difference on her 5-foot frame.
"I feel like it fell off of me," she told Insider of the weight loss. "And I don't remember changing my diet."
People who take metformin can lose from five to 15 pounds on average, as the drug changes the way the body regulates blood sugar, often decreasing a person's appetite. In short, it mimics the benefits of fasting and exercise by stimulating a key cellular cleanup and renewal process in the body called autophagy and rejiggering a person's metabolism. The most common side effect of the drug is an upset stomach.
The World Health Organization views the once-daily pill as a critical public-health tool in the fight against type 2 diabetes, listing it as one of the essential medicines that should be on hand in any well-functioning modern healthcare system.
An increasing number of doctors and scientists also have a hunch that this $5-a-month drug — derived from a compound found more than a hundred years ago in common French lilacs — could do more than help patients shed pounds and improve their blood sugar. They think it can slow down aging.
Metformin's effects on metabolism, cells, and the way our body fights viruses has drawn the interest of biohackers, academics, and clinicians, with some calling it a "wonder drug." They believe it might improve how we age, slowing the arrival of cancer, cognitive decline, and vision loss in older adults.
Bryan Johnson, a wealthy software entrepreneur who recently made headlines for his extreme anti-aging routine, said he is using the drug to prevent precancerous bowel polyps from popping up in his colon and rectum. (Some studies suggest that diabetes patients who take metformin develop fewer colonic polyps, while others show the drug may suppress colorectal-cancer growth.)
David Sinclair, a biologist and well-known researcher on aging, says in his book, "Lifespan," that he takes a gram of metformin every morning along with his yogurt with the hope it will help regulate his metabolism and keep his organs healthier and younger.
Metformin is also showing promise as a prophylactic against severe COVID and long COVID. In a large-scale study released in 2022, a group of more than 660 overweight people who took metformin as a preventative measure against the virus were less likely to get severely ill and develop long COVID than their peers. Those antiviral benefits could extend beyond COVID, too: In one large 2022 study of US veterans with pneumonia, the ones who took metformin were less likely to die.
While researchers don't yet understand exactly how metformin affects aging and disease, it's safe to say it's doing something.
Metformin is commonly used for treating diabetes via weight loss — but an anti-aging researcher believes it can do more
Carolyn Bramante, a metformin researcher who works in weight-management clinics at the University of Minnesota, says she prescribes metformin "quite often" for her patients with diabetes, prediabetes, and weight issues.
It doesn't work for everyone who wants to lose excess weight, but some patients lose up to "10% of their starting weight, or a little more," she said.
That's how Nir Barzilai first encountered metformin about eight years ago, when he was prescribed the drug to curb prediabetes and excess weight.
These days, Barzilai is leaner — and he's still taking metformin. The 67-year-old, who directs the Institute for Aging Research at the Albert Einstein College of Medicine in New York, believes the drug can serve as a kind of prophylactic for aging, helping people stay healthier, longer.
"I'm not prediabetic anymore, I'm not obese anymore, but I'm not taking out metformin," he said. "The evidence is, in my mind, so overwhelming."
In a 2020 paper he coauthored in the journal Cell Metabolism, Barzilai lays out the ways in which metformin can improve the way cells behave in an aging body. Studies suggest the drug delays stem-cell aging, encourages more autophagy, and reduces telomere shortening, all of which deter the effects of aging. The paper also provides evidence that metformin can prevent processes that encourage disease, like oxidative stress.
For all these reasons, metformin has become a daily routine not just among Silicon Valley biohackers — many well-heeled doctors are now taking the drug, too.
An infectious-disease expert takes metformin for weight management
David Boulware, an infectious disease expert who conducts research on metformin with Bramante in Minnesota, says he started taking the drug "off and on" about six months ago. He'd contracted COVID, and he knew — based on his own team's research, published in the New England Journal of Medicine in 2022 — that there was a real possibility it could have antiviral benefits. He hoped it would reduce the odds he'd have a severe case of the coronavirus and end up in the hospital.
Then he "researched it a bit more" and decided to stay on metformin for weight management. He's lost 10 pounds so far, and he'd like to lose 10 more.
Boulware isn't yet convinced there's good scientific evidence that metformin on its own can help people live longer, healthier lives. Most scientific studies of metformin for age-related issues like blurry eyesight or cancer suggest it's possible that the drug might have decent anti-aging properties, but they tend to have boilerplate language in them about how the evidence is inconclusive, or stressing that more research is needed.
The drug has shown anti-aging effects on roundworms, mice, and fruit flies, but that doesn't automatically translate to good news for humans. And almost all of the evidence for metformin's benefits for people has been done on patients with type 2 diabetes, not those with normal blood sugar.
But at the very least, Boulware thinks that maintaining a healthy weight is good for aging — and metformin can help with that.
"If you're not obese, will you live longer? Yes," he said. "Having a healthy weight is a good thing."
A major metformin study could spawn a whole new field of anti-aging drugs
Barzilai is currently working to launch a first-of-its-kind study that he's dubbed "Targeting Aging with Metformin," or TAME. He wants to conduct a large, randomized, controlled trial of 3,000 older adults at 14 medical centers around the country, to finally answer the question: Can metformin help people stay healthy and sharp in late life?
Once TAME is funded (Barzilai has raised about $23 million of the $75 million he needs for the five-year trial), it'll assess metformin's impact on the incidence of a cluster of age-related diseases, including cancer and Alzheimer's.
"We're looking at one disease at a time, not understanding that the biology of aging drives the diseases," he said. "If we can stop the biology of aging, we have less diseases. And that's a wonderful indication."
At the moment, insurance companies and FDA scientists don't recognize aging as a condition, and big pharmaceutical companies, as a result, aren't that interested in "treating" it. If successful, Barzilai's study would be the first for the FDA to consider as evidence for a new class of anti-aging drugs, called "geroprotectors," which have never been medically approved in the US before.
The regenerative-medicine scientist and aging expert Marco Quarta said that TAME could be an exciting first step toward establishing credibility for the field, as the first large clinical trial "really looking at aging as a syndrome."
"It really can pave the way for a new approach," said Quarta, the CEO and co-founder of Rubedo Life Sciences, a startup developing anti-aging medicines. "This is an exciting, emerging new field."
Taking metformin for aging has risks, especially for young people
But until there are clearer studies, Quarta thinks people should be careful with metformin for anti-aging. "It's not a magic pill," he said.
Some people lose lots of weight on metformin; others don't see an impact. It can cause rare issues like liver damage and lactic-acid buildup in the bloodstream. And it's been shown to lower testosterone and inhibit muscle growth. (One 2022 study also suggests it can harm men's sperm in a way that increases the risk of birth defects.)
"I would always suggest people be careful until we have done the studies to prove or disprove that metformin can be beneficial, and who can benefit from metformin in which conditions," Quarta said.
Barzilai himself believes that for now, off-label metformin for longevity should be limited to those already experiencing the effects of aging. "I am horrified to learn that young people (<40) without diabetes would consider taking metformin for longevity," he said in a recent tweet, echoing the concerns about the drug's effects on testosterone and muscle.
But when it comes to people of a certain age, Barzilai isn't waiting for his own trial results. He encourages his older friends and family to go ahead and ask their doctors about metformin now. Both he and his wife take it regularly.
"More and more so, the evidence is really overwhelming," he said. At this point, "I'm feeling the FDA is really a pain in the butt."
If you have an experience taking metformin off-label that you'd like to share, contact reporter Hilary Brueck: firstname.lastname@example.org
Read the original article on Insider