It’s the question many scientists are asking about the controversial drug, a glucagon-like peptide-1 (GLP-1) receptor agonist, as some studies suggest it may help people age with fewer chronic diseases. The same goes for glucose-dependent insulinotropic peptide (GIP) receptor agonists like Zepbound and Mounjaro, leaving some experts to begin looking at them as potential longevity pills and to consider how the future they can be safely prescribed to more people, especially as obesity rates continue to rise.
The single most effective and consistent way to extend lifespan in animals is calorie restriction, says Dr. Douglas Vaughan, professor of medicine at Northwestern University and director of the Potocsnak Longevity Institute. This has been demonstrated to work in 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 makes sense that it could have an effect on aging. Maybe it’s not that simple, and there could be unexpected side effects of these drugs that could negate or prevent the anti-aging effect, but it’s a big hypothesis and needs to be rigorously tested.
What are GLP-1 and GIP?
Originally, semaglutide and similar drugs were developed primarily to manage type 2 diabetes. They work by activating GLP-1 receptors and increasing insulin levels in the body, thereby lowering glucose levels. They can help suppress appetite and lose weight since GLP-1 receptors exist in the digestive system. Research shows that these drugs delay intestinal motility, slowing the rate at which 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 useful for managing or preventing some other chronic diseases and reducing systemic inflammation, although more studies are clearly needed to understand the mechanism of action.
What has research so far shown about their benefits?
A wide variety of research on GLP-1 receptor agonists and GIPs reveals that they can fight a host 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 anticancer cells known as NK cells in obese people, potentially lowering their risk of 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 Ozempics, slowed early Parkinson’s disease. Some researchers are also testing whether these drugs can prevent Alzheimer’s disease.
Even more, compelling preliminary research finds that these drugs can benefit those being treated for addiction. Animal studies, small human studies, and anecdotal reports suggest that these medications can reduce alcohol intake by curbing alcohol cravings, another lifestyle habit strongly associated with shorter lifespans and shorter health lifespans.
Most experts agree that these drugs need to be studied more extensively for each possible indication so that they can be safely prescribed outside of their FDA-approved use, which is currently for diabetes, diabetes-related heart disease and obesity.
From a purely statistical standpoint, it is likely that the number of people taking GLP-1 receptor agonists and related drugs will continue to rise, as by 2030 nearly half of all US adults are likely to are classified as obese. With this will come more chronic diseases. Currently, approximately 4 in 10 US adults 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 Albert Einstein College of Medicine, has studied the potential for repurposing a number of medications already approved by the FDA to promote longevity. He recently published an analysis in the journal Medical Research Archives that reviewed existing research on a number of drugs that appear to target 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 long-term plan for disease prevention, much in the way that people take over-the-counter supplements. He points out that it’s common practice for healthy people to take vitamins and supplements that are supposed to slow the effects of aging, especially antioxidants, even though research shows they don’t significantly affect health and we don’t know enough about their effects.
The dangers of viewing these drugs as a magic bullet
However, Dr. Barzilai cautions that GLP-1 receptor agonists are not a cure-all. I’m not here advocating that doctors give those drugs to anyone. It’s just drawing their attention to check the overall therapeutic effects of those drugs. And we must take them into account because we can and must prevent not one disease, but two or three and reduce mortality.
Doctors like Dr. Kinga Kiszko, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, cautions that these drugs are not for everyone, especially when it comes to the elderly. “A lot of times I see new diabetes agents when they do more harm than good, which is sometimes just the result of polypharmacy,” she says. Dr. Kiszko would like to see more well-designed studies measuring the impact of these therapies in older patients. There is such heterogeneity in the older adult population, there are some people who 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 means of preventing the cascading health effect of weight gain that often leads to early death. While it is recommended that clinicians reserve these medications for patients with a BMI of 27 or higher, she sometimes gives them to patients whose health is trending in a worrisome way. Maybe they don’t currently meet the criteria for being overweight or obese, but are gaining an average of 10 pounds a year, she says. Waiting another year to start medication can be detrimental to their health and increases their risk of multiple chronic diseases and early death.
I use my clinical judgment and sometimes I don’t follow the instructions, but I take other aspects into account. There have been women who don’t meet the BMI criteria to start these medications, but I still start them because I want to prevent disease instead of allowing it to happen, says Andrade, who is also a co-investigator at Mayo Precision. Medicine for Obesity. program. In my mind, it’s always case by case. I take into account the individual medical history, the family history of the 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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