A few years ago, Marc Provissiero, a film producer nearing his fifties, began reflecting on the decades ahead. He enrolled in a high-end longevity clinic, paying several hundred dollars monthly, and started monitoring his blood tests, improving his diet, and enhancing his sleep quality. His goal was to remain active as he aged—playing tennis, surfing, hiking, and spending time with his young daughter.
During Provissiero’s annual medical evaluation at the longevity clinic, his doctor, Darshan Shah, delivered a serious warning. Despite his healthy habits, Provissiero’s blood sugar levels were approaching prediabetic ranges. His family history heightened his risk for diabetes, a condition known to reduce life expectancy. When stricter diet and exercise efforts proved insufficient, Shah prescribed metformin.
Metformin has been recognized by scientists for decades for its ability to lower blood sugar. Approved by the Food and Drug Administration to treat type 2 diabetes, it is also commonly prescribed for weight loss and polycystic ovary syndrome. However, some physicians, including Provissiero’s, believe the drug might prevent a range of chronic diseases before they manifest, potentially helping otherwise healthy individuals live longer and healthier lives.
"The hope is that it leads to more healthy years," said Provissiero, who lives in Malibu, California. After taking metformin for a year, he reports feeling less bloated, having more energy, and better managing his weight and blood sugar levels.
Research on metformin’s impact on human lifespan remains limited. Much of the existing work, primarily conducted on mice, is varied and shows differing effects depending on sex and species, explained Rafael de Cabo, senior investigator at the National Institute on Aging who has studied metformin in mice for over twenty years. Human studies, mostly focused on diabetic patients, offer conflicting evidence regarding metformin’s benefits for healthy individuals.
Nonetheless, interest in metformin’s potential anti-aging effects remains high. Preliminary findings suggest it might also delay or control other conditions such as cardiovascular disease, cancer, and dementia. "Metformin could be targeting the root causes" of several age-related diseases, possibly by regulating hormones, repairing tissues, and reducing immune system inflammation, said de Cabo.
The prospect of a single medication that could "address it all" makes metformin especially appealing to those eager to prevent deadly age-related illnesses, noted S. Jay Olshansky, a public health professor at the University of Illinois Chicago.
Evidence supporting metformin’s ability to extend human lifespan is "weak but not definitively negative," added Richard Miller, a pathology professor at the University of Michigan who researches aging.
Scientists continue to investigate metformin’s molecular mechanisms. It appears to reduce cellular damage by protecting chromosomes from degradation and reversing DNA chemical tags linked to aging, among other functions, explained Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine.
Originally derived from French lilac, metformin was first formulated about a century ago to regulate blood sugar in animals. It began being prescribed for diabetes treatment in humans during the 1950s because it inhibits the body's natural glucose production and absorption, according to de Cabo.
In the early 2000s, researchers noticed that diabetic and prediabetic mice receiving metformin lived longer than healthy mice not taking the drug, suggesting it does more than control blood sugar. For instance, a 2013 study led by de Cabo found that low doses of metformin extended the lifespan of healthy male mice by around five percent, whereas higher doses shortened it. The drug’s effect resembled caloric restriction, a leading aging intervention.
Other studies have offered encouraging results. One from last year indicated that metformin slowed brain cell aging in male monkeys by up to six years. A widely cited 2014 observational study in humans found that type 2 diabetic patients on metformin had a lower mortality risk compared to non-diabetic individuals not using the drug.
However, contrasting research presents a different picture. A 2022 analysis attempting to replicate the 2014 study found no mortality benefit for diabetic patients on metformin compared to healthier individuals not taking it. There is also evidence that metformin’s benefits for non-diabetics may be temporary, reducing mortality risk for only a few years before returning to baseline.
A major national trial designed to evaluate metformin’s effects on healthy older adults has been delayed for years. The Targeting Aging with Metformin (TAME) trial, led by Barzilai, aims to compare rates of cardiovascular disease, dementia, cancer, and death in metformin users versus non-users. Due to budget constraints and interruptions, the study has yet to commence in earnest, and preliminary results are not expected for several years.
Reliable data on how many people use metformin solely for longevity purposes is unavailable. Some longevity advocates promote metformin as part of their regimen, and physicians report increasing patient requests for the drug—even from those without chronic disease risks.
Although insurance typically does not cover drugs prescribed exclusively for longevity, metformin is relatively inexpensive. Patients using it off-label often pay between $10 and $30 per month out-of-pocket.
Experts and users agree that metformin’s risks are generally minimal. Common side effects include diarrhea and difficulty building muscle, which tend to subside after discontinuing the medication. Some early longevity proponents have stopped using metformin partly due to concerns about impaired muscle growth, which they felt outweighed potential longevity benefits.
However, more serious side effects are possible. De Cabo cautioned that metformin could impair kidney function in patients with renal disease if not taken under close medical supervision.
Patients like Provissiero believe the potential benefits justify the risks. Since starting metformin, he has increased his gym visits to counteract any muscle-building challenges, though he has not yet experienced any issues.
Peter Bernard, 59, a retired tech sales executive from Haverford, Pennsylvania, has been taking metformin for about seven years. Despite never having blood sugar problems, he hoped metformin might delay the biological decline associated with aging. Bernard sees little downside to taking a 500-milligram pill twice daily, especially since he has not noticed adverse side effects. While he has not observed dramatic benefits, his blood tests and weight consistently remain within healthy ranges. He remarked, "The only way to know if it doesn’t work is to stop taking it."
Demonstrating that a drug extends lifespan could take decades, said Shah. Users like Provissiero are taking a "leap of faith" that metformin will yield long-term advantages.
While not the most powerful drug, metformin "may benefit people" struggling to keep their blood sugar or weight in a healthy range, Miller noted. It is "proven effective" in slowing the progression from prediabetes to diabetes. However, Miller emphasized that anyone claiming metformin delays aging in individuals without even the slightest sign of prediabetes should be asked to "prove it."
It is also difficult to isolate metformin’s effects. Some longevity patients take other medications and supplements believed to slow aging. Bernard, for example, also uses testosterone, whey protein, and magnesium.
Provissiero acknowledged that metformin’s greatest benefit might be prompting behavioral changes. By closely tracking his glucose and undergoing biannual lab tests for inflammation, the drug serves as a "daily reminder" that healthy eating and exercise can lower blood sugar and extend lifespan. "With lifestyle changes, I have to cooperate and behave," he said.
