METFORMIN—the first-line treatment for Type 2 diabetes— is getting new attention with the launch of the Targeting Aging with Metformin (TAME) study. The six-year study will assess the drug’s effects against three age-related diseases – dementia, heart disease and cancer—for which early research has shown some good results.
And metformin prescribed for weight loss made the pounds “fall away,” according to DC lawyer and writer D.P. In a few weeks, D.P. lost 14 pounds “without feeling hungry.” She also has “metabolic” conditions, such as high blood pressure and high cholesterol, that put her at risk for heart disease.
(Prescriptions of metformin for weight loss have been “off-label” since the FDA gave approval only for Type 2 diabetes in 1994. And because aging does not fall under the category of disease, the FDA is unlikely to grant approval for anti-aging effects of an already-licensed drug or even for a new drug.)
Long-time champion of the life-lengthening powers of metformin, Albert Einstein College of Medicine endocrinologist Nir Barzilai has been taking the drug since 2015 after a diagnosis of pre-diabetes. As scientific director of the American Federation for Aging Research (AFAR), Barzilai is leading the TAME trial.
The goal is greater resilience, especially against severe disease, said Barzilai, who believes, “Death is inevitable, but aging is not.” In past studies, diabetics who took metformin lived longer than non-diabetics who did not. Other research will assess the use of metformin to prevent the onset of frailty, which often has serious health consequences.
But metformin works differently in each patient, making its exact mechanisms of action unclear, cautioned Alan Garber, endocrinologist at Baylor College of Medicine, in 2017. “A quarter of the patient population does extremely well. Half the population does rather well, and a quarter…doesn’t do well at all.”
For adults participating in the Singapore Longitudinal Aging Studies, researchers found that taking metformin was inversely associated with cognitive impairment, with the lowest risk in those who took the drug for the longest time, more than six years.
What Type 2 diabetes, age-related conditions and weight loss have in common is chronic inflammation, which can damage cells, tissues and organs throughout the body. Chronic inflammation, as well as the body’s poor use of insulin, appear to play a role in frailty.
For diseases of aging, metformin seems to help control the body’s energy demands—mimicking the effects of a low-calorie diet in studies showing that dramatically reducing calorie intake may extend life. “The goal is not to help people live forever, but help them stay healthy longer,” according to aging researcher Steven Austad at the University of Alabama at Birmingham. “But the fringe benefit is that you live longer.”
Metformin facilitates the work of insulin to convert glucose into energy —by increasing sensitivity to insulin and decreasing insulin resistance—and reduces the production of glucose by the liver. Improved insulin sensitivity can keep blood sugar at a stable level, preventing the cravings that come with spikes and drops.
The Biggest Loser
And reducing the liver’s production of glucose decreases the chance that excess sugar will be stored as fat tissue in the body, explains Massachusetts General Hospital obesity specialist Fatima Cody Stanford, who often prescribes the medication to overweight or obese people without diabetes.
For those who struggle with weight loss, the battle is unsuccessful in many cases because of resting metabolism, which determines how many calories a person burns when at rest. On the TV show “The Biggest Loser,” most of the extremely overweight contestants who lost weight regained much if not all—and some ended up even heavier.
In subsequent research, contestants’ metabolisms not only did not recover, but some became even slower. “It is frightening and amazing,” said metabolism specialist Kevin Hall at the National Institutes of Diabetes and Digestive and Kidney Disease. One contestant regained more than 100 pounds, his metabolism slowing to the point that he must now eat 800 calories a day less than a typical man his size to avoid putting on additional pounds.
Metformin, however, is not a good option for everyone. In addition to decreased appetite, side effects include nausea, stomach upset and diarrhea. Some doctors require frequent blood-sugar testing for patients on metformin, though others believe the drug keeps sugar levels stable enough that testing is unnecessary. Finally, some people who lose weight on metformin must stay on the drug to avoid future weight gain.
Getting a Prescription
Because metformin affects blood sugar and weight, some people interested in its anti-aging possibilities may have trouble obtaining a prescription if these issues are not a problem. The diagnosis of Type 2 diabetes requires blood levels of hemoglobin A1c (or AIC) at 6.4% or higher. While some physicians want to start treatment for “pre-diabetes” —AIC levels between 5.7% and 6.4%—others contend that “pre-” disease, including others like osteopenia, means no disease at all.
In addition, most physicians don’t want to prescribe any drug for pre-diabetes in those over age 60 because blood sugar levels in the majority of these patients will either remain stable or revert to lower “normal” levels, according to research from Sweden and elsewhere.
Metformin is also available online after a “consultation.” And once the TAME trial begins, volunteers could receive the drug. A concurrent trial, TAME BIO, will search for indicators or biomarkers of aging — to provide diagnostic grounds for future metformin prescriptions.
Florida lawyer L. M., who is thin, in good shape and has a healthy diet, asked her doctor to prescribe metformin for dementia (about which she worries but has no symptoms); she does have a familial risk for diabetes, as well as high total cholesterol levels. But concern about side effects as well as L.M.’s insufficiently high blood-sugar levels led her doctor to prescribe instead only a statin for the cholesterol.
Despite worries about GI side effects, I would take metformin if my doctor were willing to prescribe it but am reluctant to go the online route. And if given the chance, I will volunteer for the TAME trial—for the value of being carefully followed during the aging process, with the added hope of obtaining metformin’s benefits.
Mary Carpenter regularly reports on topical issues in health and medicine.