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America is embarking on a risky experiment with GLP-1s and aging

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More than one in 10 Americans takes a GLP-1 medication for weight loss. As more people take a GLP-1, or glucagonlike peptide 1, receptor agonist, such as Wegovy, so, too, do more older adults—and those numbers are set to skyrocket.

Last week the Trump administration launched the Medicare GLP-1 Bridge program, a new initiative that would set the cost of three weight-loss medications— Wegovy, the KwikPen version of Zepbound (tirzepatide) and Foundayo (orforglipron)—at $50 a month. That may be welcome news for the estimated 38.9 percent of adults aged 60 and up in the U.S. who are living with obesity. But it could also supercharge an ongoing and risky experiment in growing old on weight-loss drugs.

For years, clinicians have had few good options to safely treat obesity in older adults. But while GLP-1s, long used to treat diabetes, are now approved for weight loss, the evidence supporting their use in the age-60-and-older population is limited. Someone in their 70s may benefit as much from weight loss as a person in their 30s but may respond very differently to these drugs’ side effects; we simply don’t have enough evidence yet to make informed conclusions, experts advise.

“Eligibility doesn’t mean benefit automatically,” says Ruchi Gaba, an associate professor of endocrinology at Baylor College of Medicine. “We have to individualize.” And within the 60-and-older group, there is huge variety: a healthy, active 68-year-old with obesity and sleep apnea is a very different patient than an 88-year-old who’s frail, has poor appetite and is at risk of falls, Gaba says.

Older adults are underrepresented in the clinical trials for GLP-1 drugs. Despite the high prevalence of obesity among this age group, only about one in 10 participants in early GLP-1 trials was age 65 or older, says Alissa Chen, a primary care physician and a researcher at the Yale School of Medicine, who specializes in obesity. Older adults are more heterogeneous than people in younger age groups in terms of chronic conditions and multiple medications, Chen says, which can pose challenges with both prescriptions and side effects.

“We need to be more critical about who we’re starting on these medications and thinking about all those chronic conditions and thinking about those medicines, thinking about the benefit there is to be gained,” she says. “We have to think about ‘What does weight loss get us in that age group?’”

GLP-1 drugs work by mimicking the glucagonlike peptide 1 hormone, which the body naturally releases after eating to signal satiety. The hormone stimulates insulin secretion, suppresses glucagon—preventing the hormone from causing the liver to release too much sugar into the bloodstream —and slows gastric emptying. These effects create a prolonged feeling of fullness that drives weight loss.

GLP-1s don’t tend to interact with other drugs directly, but their effects can create cascading risks, Gaba says. Slow gastric emptying can worsen constipation—a common complaint in older adults. It can also cause nausea and vomiting, which can lead to dehydration. In turn, dehydration can cause orthostatic hypotension and falls in people who also take medications for blood pressure. Diabetic patients taking a sulfonylurea, a class of medications that lower blood sugar, have heightened hypoglycemia risk on GLP-1s, Gaba says.

Lean muscle loss is another well-known side effect of GLP-1s. That could make older adults more at risk of serious injury if they fall. At the same time, older patients may respond to medications differently than their younger counterparts because of their body composition and reduced liver and kidney function.

Functional ability, rather than a number on a scale, should be the determining factor in whether to prescribe a GLP-1 or not, Chen says. “Success for a senior might mean being able to walk longer distances without knee pain or getting on the floor to play with their grandchildren,” she says. “If a senior loses weight but also loses significant muscle mass, is the treatment really a success?”

GLP-1s are meant for indefinite use—otherwise the weight returns. The new Trump administration Medicare program is temporary; it currently runs for just 18 months. But once someone starts taking one of these drugs, stopping is far from ideal, Chen says. “These are medications that should be taken for the long term.”

If a person is already eating well and exercising, Chen says, she’s often reticent to prescribe a drug that will make them lose more weight. “We know exercise is very good at keeping people healthy and helping them live long and improving cardiovascular fitness,” she says.

The purpose of weight loss is to do that same thing. But if a patient is already making choices that improve those things, “it’s questionable to me how much more weight loss will help them,” Chen adds.

For patients with other underlying conditions, there’s evidence that GLP1s can improve healthspan, which in turn may affect lifespan. In those older than age 65, however, lifestyle interventions remain the first line of obesity management.

Although GLP-1 drugs are often used as long-term maintenance therapy because stopping them commonly leads to weight regain, there is still limited data on their effects over a full lifespan in older adults, especially frail older adults. Analyses to date show that, in older adults, GLP-1 drugs are associated with fewer cardiovascular events and, in some studies, lower all-cause mortality. But there is no direct evidence that they extend lifespan.

Chen’s research shows that side effects can affect as many as 40 percent of people taking weight-loss drugs. Older adults tend to abandon treatment because of these effects. And when they do, they regain lost weight, which can worsen any underlying health conditions such as cardiovascular disease or type 2 diabetes.

Resistance exercises and higher protein intake could ensure some of that regained weight is in the form of muscle, not fat. But “if you’re not doing those things, you could be having higher adiposity after than you were before you ever started the medication,” Chen says.

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Click the link below for the complete article:

https://www.scientificamerican.com/article/america-is-embarking-on-a-risky-experiment-with-glp-1s-and-aging/

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