With the holidays past and the new year arrived, we look ahead — to losing weight. For some that resolve theoretically involves dieting or gym memberships, but for increasing numbers of overweight adults (roughly three-fourths of us) there is another option: GLP-1 drugs with names like Ozempic, Wegovy and Rybelsus, with a mean weight loss of 15% to 25% at 1-1.5 years of use.
But weight, there’s more to the story.
GLP-1 is short for glucagon-like peptide-1, a natural hormone that helps regulate blood sugar, slow digestion and reduce appetite. GLP-1 drugs are designed to mimic the hormone’s functions.
The drugs were originally developed to treat type 2 diabetes, but their dramatic weight loss effects have made them far more popular for treating obesity. Last year, 12% of U.S. adults reported taking a GLP-1 drug, according to one poll; 6% said they were currently on one.
In 2024, Ozempic, Rybelsus and Wegovy (semaglutide) were the most popular drugs in the country, based on sales. In the next few years, the GLP-1 market is expected to exceed $100 billion annually, with perhaps dozens of these drugs on the market.
They come with a risk of side effects, including nausea, vomiting, diarrhea and constipation, and, more rarely, pancreatitis, kidney damage, retinopathy and medullary thyroid cancer.
More worrying are potential long-term health risks. Some research suggests GLP-1 drugs may be associated with sarcopenia, a loss of muscle mass and strength that can become a significant health problem as we age. But Dr. Sam Klein, a noted researcher on nutritional science and obesity at Washington University School of Medicine in St. Louis, isn’t so sure. “The current data do not show that weight loss in people with obesity has an adverse effect on physical function,” said Klein. “In fact, weight loss improves physical function because the relative decrease in muscle mass is always less than the relative decrease in fat mass, so the ratio of muscle mass to body weight increases.
The fact is, we simply don’t know yet what the long-term effects of GLP-1 drugs are, which patients must currently take daily or weekly achieve and maintain results. If they stop, the pounds tend to return, which can be unhealthier than the original weight.
If GLP-1 drugs prove to have long-term health risks, they wouldn’t be unique.
Proton pump inhibitors (PPIs), for example, are a class of drugs that reduce stomach acid and treat conditions like heartburn, gastritis and peptic ulcer disease. When they debuted in 1988, they quickly became popular with brand names like Prilosec, Prevacid and Nexium. Current market sales exceed $3 billion annually.
Most people who use a PPI experience only mild side effects, such as dry mouth or headaches, or none at all. But long-term use can increase the risk of serious medical conditions, such as an impaired immune system, greater likelihood of bone fractures and chronic kidney disease. As a result, doctors usually prescribe PPI dosages for the shortest time possible to improve symptoms, but not increase risk of potential side effects.
This is quite different from, say, statins, widely prescribed for high cholesterol and cardiovascular health. Like GLP-1s, statins must be taken indefinitely to achieve and maintain their health benefits, but years of research have shown that they are remarkably safe with extremely low risk of adverse consequences.
More research and development will likely improve the safety and efficacy of GLP-1-based drug therapies. New and better weight loss compounds may be discovered. But in the meantime, we need to consider whether these medications are currently overused.
One remedy might involve more effectively incorporating tried-and-true efforts like healthy eating, exercise and better lifestyle choices with medications.
We can dream of a no-sweat fix to obesity, but the biological reality is that a good life begins and ends with a healthy diet and regular exercise. Not as easy to swallow as a magic pill, but probably better for you.