A cheap, readily available medication recently has been hailed as a wonder drug – capable of protecting against everything from diabetes to heart disease, to cognitive decline and cancer.
So, what is metformin? And is there any truth to the hype of it?
To find out, we spoke with Dr. Greg Schwartz.
Schwartz, who has both medical and doctorate degrees, is a professor at the University of Colorado Anschutz Medical Campus and chief of cardiology at the Rocky Mountain Regional Veterans Affairs Medical Center in Aurora.
What is metformin?
Metformin is one the most commonly used drugs on the planet, Schwartz said. More than 200 million people are estimated to be taking it across the globe every day, mostly to treat or prevent 2 diabetes.
It’s also been around for a very long time.
“Metformin really goes back centuries,” Schwartz said. “It was used as an extract from the French lilac plant in the 1700s, and people learned that it helped to control what they called back then sweet urine disease – what we would now call diabetes,” he said.
It wasn’t until the 20th century that the active ingredient in the botanical extract was purified and characterized as metformin. A French physician named Jean Stern did the first tests of metformin in humans back in the 1950s and found that it helped to lower blood sugar. (For the crunchy readers who love an herbal remedy: Schwartz said you can’t substitute a botanical for a well-defined, quality-controlled pharmaceutical product.)
“Metformin was approved for use in treating diabetes in Europe back in 1958, so we’re talking 66 years of use,” Schwartz said.
What does metformin do?
Metformin is broadly known to improve the way the body handles insulin, which then lowers blood sugar levels.
It’s generally well tolerated, though some common side effects can include abdominal discomfort, decreased appetite, diarrhea, muscle pain or cramping, sleepiness and more. One study published in the Journal of Research in Medical Sciences called the adverse, or undesired, effects of the medication “negligible” when compared to the benefits.
Some studies even show it reduces the risk of blood, urologic, and gastrointestinal cancers, though results have been mixed.
So, what’s the truth about metformin? Does it work to fight diseases? If so, which ones?
Metformin has long been established as a way to treat and prevent type 2 diabetes.
Because of the way it impacts insulin, it can also be used as a treatment for polycystic ovary syndrome (PCOS), a set of symptoms caused by a problem with a woman’s hormones, one of which can include infertility. According to a study published in the Annals of Translational Medicine, metformin can effectively induce ovulation in some women with PCOS.
What diseases do doctors think metformin might treat?
That’s where Schwartz’s research comes in.
Metformin works by activating an enzyme called AMPK, which is essentially a sensor that regulates cellular metabolism.
“The AMPK enzyme serves to protect cells against a variety of stresses,” Schwartz said. “In the liver, its activation is what’s responsible for the control of blood sugar, but in other tissues in the body, the activation of AMPK by metformin may protect those cells and increase their defense against various kinds of stressors.”
Experiments done on animals over the last two decades showed that metformin was protective in the cardiovascular system, Schwartz said. That explains why cardiologists are involved in research on a medication that is primarily used to treat diabetes.
Metformin reduced the severity of a heart attacks in animals and improved the function of blood vessels and the lining of cells inside the blood vessels called endothelial cells, Schwartz said. In a variety of animal species, metformin helped animals with and without diabetes live longer.
Of course, research results in animals don’t always translate to humans, but Schwartz and others are hopeful that metformin might have other benefits.
“It raises the question of whether metformin might have broader uses beyond treating blood sugar in diabetes and actually be a drug that can help protect the body in people without diabetes,” Schwartz said.
If metformin has so many applications, why are we just finding out about them now?
“Metformin has been a generic drug for many, many years,” Schwartz said. “There’s not been a great deal of interest by pharmaceutical companies to test the hypothesis that metformin actually protects against things like heart attacks, strokes, and other blood vessel problems.”
In 66 years of use, Schwartz said, there hasn’t been a double-blind, randomized clinical trial – the gold standard of research. In such a trial, half of patients are given a treatment, such as metformin, and half given a placebo. Neither the patients, doctors, nor the research team knows who got what treatment until the end.
“Recognizing that we had this gap in our knowledge with a very important drug, a promising drug, but one that really hadn’t been put through the proper tests, the VA decided to fund a large clinical trial to test whether metformin is actually a protective drug in what we call prediabetes,” Schwartz said.
Schwartz is leading the study for the U.S. Department of Veterans Affairs (VA), which will include about 40 VA centers across the country, including the Rocky Mountain Regional Veteran’s Administration Medical Center.
Eventually, it will enroll about 7,400 veterans with prediabetes who already have cardiovascular disease, Schwartz said.
“We’ll test whether metformin, compared to the placebo group, reduces those people’s risk of having a heart attack, stroke, or dying,” he said. “The studies began last year, in 2023, and we’re making very good progress. Hopefully this will be an important contribution to our medical knowledge.”
So, is metformin a miracle drug?
“There’s been some hype about metformin (claiming) that it’s a drug that will be the anti-aging, longevity drug that will prevent all the things that happen to us as we get older from heart disease, to cancer, to neurodegenerative disease,” Schwartz said. “And of course, if that were true, it would be fantastic. But realistically, I think we have to take it one step at a time.”
It would be premature, he said, for people to go out and start taking metformin or asking their doctor to prescribe it without the evidence to support its use outside of type 2 diabetes and a couple of specialized conditions.
How is metformin different from semaglutides like Ozempic and Wegovy?
Metformin works on different pathways than drugs like Ozempic, Wegovy, Mounjaro and Zepbound, Schwartz said, though semaglutide can also reduce many of the same health problems as metformin.
“Semaglutide is a fantastic drug with high quality evidence to show its effectiveness,” Schwartz said. “So, consequently, in American Diabetes Association guidelines, drugs like Ozempic have risen to the top of the recommendations for treatment in people who have diabetes and also have cardiovascular disease.”
Metformin used to be at the top of the list, Schwartz said. For now, it’s good advice to use semaglutides, he said, because they’ve been proven to work.
If Schwartz and his team can provide the same kind of high-quality evidence through their trial that metformin can do those things, metformin, which can cost less than a dollar a day, may move back up to the top of the list.
“Then we would have a drug that’s far less expensive and would provide hopefully similar benefits,” he said. “But that still remains to be proven.”
Does metformin cause weight loss?
According to the Cleveland Clinic Journal of Medicine, metformin can support weight-loss in adults with obesity and without type 2 diabetes, though the FDA has not approved the drug for this use because the results tend to be modest and inconsistent. Some evidence suggests metformin helps with weight loss by reducing appetite and changing the gut microbiome.