Diabetes drug metformin proves useful for other problems

Diabetes drug metformin proves useful for other problems
Karen Weintraub
USA TODAY
July 30, 2013

Early research suggests the decades-old diabetes drug metformin can slow cancer, reduce heart disease and perhaps limit the ravages of Alzheimer's. A new study shows it can extend lifespan in mice.

Could metformin, the most widely used diabetes drug in the world, be useful for fighting a number of health problems?

Early research suggests the decades-old drug can slow cancer, reduce heart disease and maybe even limit the ravages of Alzheimer's. Now, a new study in mice finds that it can extend life by a number of weeks — the human equivalent of 3-4 years.

It's far too soon for healthy people to consider taking the drug, researchers say, but the findings are provocative, and suggest science is getting closer to a day when it may be possible to pop a pill to live healthier longer.

Diseases of aging, like cancer, heart disease, type 2 diabetes and dementia are all linked along a biological pathway, researchers say. Eating less food appears to trigger that cascade, significantly extending life in animals, probably by slowing down metabolism.

Metformin is the third drug shown in early research to affect the same pathway, along with rapamycin, a powerful medication used to prevent rejection of transplanted organs; and resveratrol, a compound found in red wine.

"It's clear that we are edging toward developing a pharmaceutical intervention that is going to be able to delay or postpone aging," said Rafael de Cabo, a biogerontologist at the National Institute of Aging, who conducted the new mouse study, published today in Nature Communications. "For how much and how long I have no idea."

Brian Kennedy, CEO of The Buck Institute for Research on Aging in Novato, Calif., said he envisions a day when, instead of giving people drugs after they get sick, healthy people will be able to take pills to avoid illness. Such a pill wouldn't prevent all aging, he said, but by delaying the deadliest diseases for even a few years, it could have a dramatic benefit on an individual's quality of life and the nation's economy.

Despite their optimism, both Kennedy and de Cabo said that healthy people should not be taking metformin at this point. While mice are a good model for diseases, they do not respond exactly as people do; and they live a totally controlled life inside a cage, de Cabo said.

Metformin caused severe kidney problems in mice taking a high dose, suggesting that researchers need to proceed with caution when testing the drug in people, de Cabo said. Even the low dose used in his study left mice with more drug in their bloodstream than diabetics get on their metformin regimen, so it's not yet clear what dose to use in healthy people.

The drug is also known to cause diarrhea, because it affects the metabolism of sugars in the digestive system.

So far, those two side effects have kept researchers from trying the drug on themselves. David Sinclair, a genetics professor at Harvard Medical School who has done extensive research on resveratrol, said he took metformin along with his resveratrol for a short time. He stopped when he saw the toxic effects in this mouse study, which he co-authored. He said he wouldn't take rapamycin because of its side effects.

A new drug will eventually be developed, he predicted, that will amplify the benefits of these drugs and minimize their side effects.

"In terms of history, we're still at the very early stages of understanding how to slow aging in a safe way," said Sinclair.

Even if it turns out not to extend life, metformin has shown powerful results in other areas of research:

• Kevin Struhl, a molecular and cancer biologist at Harvard Medical School, said he has been impressed by early studies showing metformin's effectiveness at treating cancer and stopping cells from turning cancerous in the first place.

• At the University of Pennsylvania, Alzheimer's expert Steven Arnold is studying the drug's ability to slow or prevent mental decline.

• And other work has shown that metformin can help stop pre-diabetes before it turns into type 2 diabetes, said Karin Hehenberger, a molecular biologist, diabetes expert and chief medical officer at Coronado Biosciences, a Massachusetts biotech company focused on autoimmune diseases.



In terms of aging, we already know enough to help people until a pill can be developed, Kennedy said.

"There's a huge secret to (combating) aging right now," he said. "That's eat right and exercise."