Metformin: Science finds new benefits from an old drug

NEW YORK, Aug. 25 (UPI) — Medical science continues to develop new and innovative ways to boost health and well-being, but a relatively old drug — metformin — may hold the key to human longevity and preventing life-threatening illness, experts told UPI.

Used to treat Type 2 diabetes since the 1950s, metformin has in recent years been touted as a preventative medication for everything from dementia and heart disease to certain types of cancer.

Although the drug has been around for decades, relatively recent research has identified those potential benefits.

This research has been spurred, at least in part, by similar benefits associated with another class of drugs for Type 2 diabetes and/or weight loss, GLP-1 receptor agonists.

These drugs, like semaglutide, which is marketed as Rybelsus for Type 2 diabetes and Wegovy for weight loss, and tirzepatide, or Mounjaro, lower blood sugar and boost weight loss, which in turn improves the overall health of those taking them and lowers their risk for heart disease and other life-threatening conditions.

“Metformin is a very old drug, and it has been the drug of choice [for] diabetes since the 1950s,” said Dr. Jawahar L. “Jay” Mehta, chair of the Division of Cardiology at the University of Arkansas for Medical Sciences in Little Rock.

However, “recently it has become apparent that metformin has several other” potential benefits, Mehta told UPI in an email.

Derived from a plant

How and why does this older drug potentially hold the key to long-term health?

Metformin is derived from the plant Galega officnialis, more commonly known as galega or goat’s-rue, which is naturally found in parts of northern Africa, western Asia and Europe, but is widely grown elsewhere, Mehta said.

Used as a medicinal herb for digestive health and to treat urinary problems and other health conditions for centuries, it was discovered just over a century ago that it could lower blood sugar, according to Harvard Health.

The resulting drug was approved for use in people with Type 2 diabetes in Europe in the 1950s, and was cleared for the same purpose in the United States by the Food and Drug Administration in 1995.

Metformin belongs to a group of drugs called biguanides and it works as a potent antidiabetic drug by decreasing glucose production in the liver, Mehta said.

“It reduces glucose absorption from the intestines and improves insulin sensitivity in the body,” said Mehta, who published a study in June highlighting the drug’s other effects on the body that may yield health benefits.

Among them are activating adenosine monophosphate protein kinase, a substance that stimulates energy in the body’s cells and is involved in metabolism, which could explain why the drug helps with weight loss, he said.

Metformin also may reduce the body’s production of reactive oxygen species, which are molecules derived from oxygen, Mehta said.

“Many of these effects can be explained by control of blood sugar, but the other effects of metformin … may also explain its significant and unique cardioprotective effects,” he added.

High levels of reactive oxygen species can overwhelm the body’s antioxidant defenses, leading to oxidative stress and potentially causing heart failure, atherosclerosis, or the buildup of fats, cholesterol and other substances along the artery walls, and other heart problems.

“Dementia and chronic pain are thought to be related to excess reactive oxygen species generation and inflammation,” Mehta said.

“It is possible that metformin improves these disease entities by reducing reactive oxygen species,” he said.

Metformin and cancer

In adults age 50 years and older, metformin may also lower levels of insulin-like growth factor 1, a hormone involved in bone and muscle development, researchers found.

Although beneficial for growth in children, the hormone in elevated amounts have been linked with an increased risk for breast, colon and prostate cancer.

“Pre-clinical studies have shown that metformin can interact with important and relevant proteins and ultimately prevent cancer cell growth,” Dr. David J. Benjamin, a medical oncologist at the Hoag Family Cancer Institute in Newport Beach, Calif., told UPI in an email.

“In addition, observational studies involving large groups of individuals with different cancers, such as lung cancer, have suggested that those who took metformin lived longer than those who did not take metformin,” he said.

Metformin miracle?

So, is metformin a miracle drug? Should everyone use it to improve health and, potentially, live longer? Not yet, according to the experts.

“Some physicians strongly believe in the ‘good’ effects of metformin and prescribe this drug to modify aging, but there is no scientific proven basis for this approach,” Mehta said.

The potential health benefits of metformin means the drug “may play a role in longevity … but there is a lack of high-level evidence data in humans to demonstrate whether this is true or not,” Benjamin said.

“It would be challenging to run a clinical trial given there are many factors that play a role in an individual’s longevity, such as pre-existing medical conditions, past social and environmental exposures, and genetics, among others,” he said.

The drug may also interact with certain cancer therapies, meaning people who already have cancer and are being treated for it could have problems taking it, Benjamin added.

There also the potential of side effects with metformin, which include abdominal or stomach discomfort, cough or hoarseness, decreased appetite, diarrhea, general feeling of discomfort, lower back or side pain, and muscle pain or cramping.

Up to 6% of people who take metformin and develop diarrhea lasting more than a week may lack the “transporters” needed for the drug to be sufficiently absorbed by cells in the body for it to work effectively, according to geneticist and endocrinologist Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York.

In addition, people younger than 50 who don’t have Type 2 diabetes shouldn’t take metformin because they still need insulin-like growth factor 1 for healthy muscle and bone development, he said.

Still, for those over age 50 years, the aging benefits of the drug may soon have more scientific evidence supporting them, as he and his colleagues are starting work on clinical trials designed to persuade the FDA to approve it as a treatment for aging, Barzilai told UPI in a phone interview.

That process will take several years, but Barzilai said he already has anecdotal evidence that the drug improves healthy aging — his 87-year-old aunt convinced her doctor to prescribe the drug, “even though she is thin and doesn’t have diabetes,” and she has noticed some benefits.

“For years, she used to get the flu and get terribly sick — she stopped getting the flu after starting metformin,” Barzilai said.

He added: “There are 12 hallmarks of healthy aging, including things like immune health, and we are learning that metformin targets all of them.”