Two of the hottest trends in health — longevity medicine and weight loss drugs — are colliding.
A theory that GLP-1 medications like Ozempic or Zepbound might help people live longer has been bandied about by biohackers and aging researchers for several years. Online pharmacies already market compounded versions of the drugs to purportedly extend health span. But so far, academic research into the hypothesis has been scant.
One of the first studies putting the idea to the test was published last month. It showed that, among people with H.I.V. and lipohypertrophy (fatty deposits that develop under the skin), taking semaglutide (the drug in Ozempic) for eight months seemed to slow participants’ biological aging, according to blood tests that measure age-related biomarkers. People with H.I.V. experience accelerated aging because of the infection, so they are a good population in which to conduct age-related research, said Michael Corley, an associate professor of medicine at the University of California, San Diego’s Stein Institute for Research on Aging, who led the study.
The trial was preliminary, but it “provided us an opportunity to say, hey, is there any signal here that warrants all the hype?” Dr. Corley said.
That hype stems from several lines of evidence. First, there is ample research demonstrating that GLP-1s improve people’s metabolic health by helping to regulate insulin and blood sugar levels and causing weight loss. Several studies show that they also benefit cardiovascular, liver and kidney health.
Because the drugs offer protection for conditions like diabetes and cardiovascular disease, which are both among the leading causes of death, it could already be reasonable to call GLP-1s longevity drugs.
“GLP-1 agonists decrease the incidence of diseases that are related to aging and are associated with decreasing life span,” said Dr. Nicolas Musi, the director of the Diabetes and Aging Center at Cedars-Sinai in Los Angeles. “One would assume that they’re also potentially going to increase life span and be beneficial for longevity,” he added.
Another reason experts think these drugs might increase longevity is because of how they affect cellular health. Metabolic health and aging are intricately linked, so drugs that alter the mechanisms involved in metabolism may also affect how the body ages.
“Many of these pathways that are modulated by diabetes drugs are also central pathways that control aging and longevity,” Dr. Musi said. (Other drugs that treat diabetes, like metformin and a category known as SGLT2 inhibitors, are similarly being studied for longevity, though the evidence so far has been mixed.)
GLP-1s appear to influence other fundamental cellular changes that occur with aging, most notably inflammation. “We know they have a significant anti-inflammatory effect, and we know inflammation is one of the things that accelerates aging,” said Dr. Thomas Blackwell, a professor of general internal medicine at the University of Texas Medical Branch in Galveston.
All of this sounds promising, but researchers say there’s a huge caveat: Currently little to no data exists on whether the drugs will benefit people who are metabolically healthy.
There is not even data available about whether the medications extend life span in healthy rodents. Dr. Richard Miller, a professor of pathology at the University of Michigan, who runs a large program there testing potential anti-aging drugs in mice, said that’s mainly because of logistics. The currently available GLP-1s either don’t work in mice the same way they do in humans, or they can only be delivered via injection, and years of weekly injections in mice aren’t practical.
There are also concerns that GLP-1s negatively affect health in ways that are especially relevant for aging. Most notably, the drugs can cause some muscle loss, a major issue for older adults that is associated with an increased risk of frailty. Rapid weight loss can also lead to a decline in bone density and an increased risk of osteoporosis.
A few clinical trials that are testing GLP-1s on several biomarkers of aging, like inflammation levels and biological age clocks, as well as on functional abilities like strength and walking speed, are finally getting underway. At least one of the studies still will not be conducted on healthy older adults, though, since the participants need to meet the criteria for receiving a prescription for the weight loss medications, said Dr. Blackwell, who is leading the trial. But he added that those criteria — for example, a body mass index of 27 or greater and a related health condition, like hypertension — reflect “a whole lot of Americans.”
For now, experts generally don’t recommend taking the medications off label for longevity. “In patients that are otherwise healthy, at this point, I think it’s premature, because there are no data justifying it from preclinical or clinical studies,” Dr. Musi said.
In Dr. Blackwell’s case, the message seemed to be, do as I say, not as I do. He has been taking tirzepatide (the drug in Zepbound) for the past year with the goal of slowing aging.
“Do I know that that’s the right thing? I do not,” he said. “Do I recommend that for patients? I do not.”
“This is my own personal decision,” he added.