It’s the question many scientists are asking about the controversial drug, a glucagon-like peptide-1 receptor agonist (GLP-1), as some research suggests it could help humans age with less chronic diseases. The same goes for glucose-dependent insulinotropic peptide receptor agonists (GIP) such as Zepbound and Mounjaro, leaving some experts to start seeing them as potential longevity pills and considering how in the future they can be prescribed safely to more people, especially as rates of obesity continue to rise.
“The singular most effective and consistent way of extending lifespan in animals is caloric restriction,” says Dr. Douglas Vaughan, a professor of medicine at Northwestern University and director of the Potocsnak Longevity Institute. “That’s been demonstrated to work on everything from worms to flies to mice to monkeys. If you can find a way to get people to chronically reduce their caloric intake, it sort of makes sense that it might have an effect on aging. It’s probably not as simple as that and there could be unexpected effects of these drugs that might negate or prevent the anti aging effect, but it’s a great hypothesis and it needs to be tested rigorously.”
What are GLP-1s and GIPs?
Originally, semaglutide and similar drugs were primarily developed to manage type 2 diabetes. They work by activating GLP-1 receptors and increasing insulin levels in the body and thereby decreasing glucose levels. They can help with appetite suppression and weight loss since GLP-1 receptors exist in the digestive system. Research shows these drugs delay gut motility, slowing how quickly food is digested and curbing hunger and food cravings.
However, GLP-1 receptors also exist in organ systems throughout the body such as the kidneys, heart, blood vessels, and of course, the brain. This may be why they prove beneficial for managing or preventing several other chronic diseases and reducing systemic inflammation, though undoubtedly more studies are needed to understand the mechanism of action.
What has research shown so far about their benefits?
A wide variety of research on GLP-1 and GIPs receptor agonists finds they may combat a constellation of chronic and age-related diseases including heart disease, nonalcoholic fatty liver, disease, kidney disease, sleep apnea and polycystic ovarian syndrome. Some preliminary research also finds that semaglutide, a type of GLP-1 therapy, restored the function of anti-cancer cells known as NK cells in people with obesity, potentially lowering their risk for certain types of cancer.
These drugs also appear to have neuroprotective benefits. A small study published in April in the New England Journal of Medicine found lixisenatide—another GLP-1 receptor agonist and close cousin of Wegovy and Ozempic—slowed early Parkison’s disease. Some researchers are also testing whether these drugs can prevent Alzheimer’s disease.
Even more, compelling preliminary research finds these drugs could benefit those in treatment for addiction. Animal studies, small studies on humans and anecdotal reports suggest that these medications can lower alcohol intake by curbing alcohol cravings—another lifestyle habit strongly associated with shorter lifespan and healthspan.
Most experts agree that these drugs would need to be studied more extensively for each potential indication in order to safely prescribe them outside of their FDA-approved usages, which is currently for diabetes, diabetes-related heart disease and obesity.
Purely from a statistical standpoint, it is likely that the number of people taking GLP-1 receptor agonists and related drugs will continue to increase, since by 2030 nearly half of all US adults will likely classify as obese. With that will come more chronic disease. Currently, roughly 4 in 10 adults in the US live with two or more chronic diseases, according to the US Centers for Disease Control and Prevention.
Dr. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine, has been studying the potential for repurposing a number of already FDA-approved medications to promote longevity. He recently published an analysis in the journal Medical Research Archives that reviewed the existing research on a number of drugs that appear to target the twelve hallmarks of aging such as mitochondrial dysfunction, cellular senescence and telomere shortening. GLP-1 receptor agonists made the shortlist after SGLT2 inhibitors, metformin and the osteoporosis drug, bisphosphonates.
Dr. Barzilai envisions a future where semaglutide and these other drugs are part of a longer term plan for disease prevention, much in the way people take over-the-counter supplements. He points out that it’s a common practice for healthy people to take vitamins and supplements that are purported to slow the effects of aging, specifically antioxidants, even though the research demonstrates that they don’t significantly impact health and we don’t know enough about their effects.
Risks of seeing these drugs as a magic bullet
However, Dr. Barzilai cautions that GLP-1 receptor agonists are not a cure-all. “I’m not here calling for doctors to give those drugs to anyone. I’m just calling their attention that we check the general therapeutic effects of those drugs. And we have to consider them because we can and we should in order to prevent, not one disease, but two or three and to decrease mortality.”
Physicians like Dr. Kinga Kiszko, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, caution that these medications aren’t for everyone, especially when it comes to older people. “A lot of the times where I see the new agents for diabetes is when they do more harm than good, which is sometimes just a result of polypharmacy,” she says. Dr. Kiszko would like to see more well-designed studies that measure the impact of these therapies on elderly patients. “There’s such heterogeneity in the older adult population, there are some people who we absolutely do not want to lose weight.”
Dr. Maria Daniela Hurtado Andrade, an assistant professor of medicine and endocrinologist at the Mayo Clinic, is already prescribing semaglutide as a tool to prevent the cascading health effect of weight gain that often leads to early death. While it’s recommended that clinicians reserve these medications for patients with a BMI of 27 or greater, she sometimes gives them to patients whose health is trending in a concerning way. Perhaps they do not currently meet the criteria for being overweight or obese, but they are gaining an average of 10 pounds annually, she says. Waiting another year to start the medication could prove detrimental to their health and up their risk for multiple chronic diseases and early death.
“I use my clinical judgment and sometimes do not adhere to the guidelines, but consider other aspects. There have been women who do not meet criteria by BMI to start these medications but I still start them, because I want to prevent disease instead of letting this happen,” says Andrade, who is also a co-investigator at the Mayo Precision Medicine for Obesity program. “In my mind, it is always case-by-case. I take into account the individual medical history, family history of risks of using these medications and then I discuss all these aspects with patients and my patients make an informed decision at the end of the day.”
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