Long-term safety questions mount as GLP-1 drugs move into mainstream weight management

As GLP-1 medications become a common treatment for weight loss and diabetes, experts highlight promising benefits but warn of unresolved safety concerns, especially around long-term use and discontinuation risks amid rising costs and access challenges.

GLP-1 medicines are moving from diabetes clinics into the centre of everyday conversation, fuelled by their rapid rise as weight-loss drugs and by the public fascination around what they can, and cannot, do. The question now facing patients and doctors is not whether they work in the short term, but how safe they are when taken for years. Research and expert commentary suggest the picture is encouraging but still incomplete, with important questions left about long-term use, stopping treatment and who should take these drugs in the first place.

GLP-1 stands for glucagon-like peptide-1, a hormone-linked treatment that helps regulate blood sugar and appetite. Jaime Almandoz, a professor of internal medicine and medical director of the Weight Wellness Programme at UT Southwestern Medical Center, said these medicines help people feel satisfied with less food for longer, which is why they have become a major option for type 2 diabetes and chronic weight management. He pointed to the 2023 SELECT trial, which found that semaglutide reduced major cardiovascular events by about 20% in adults with obesity, underscoring that the drugs can offer benefits beyond weight loss alone.

But the long-term safety picture is still developing. Almandoz said it is reasonable to ask what will become clear after much longer exposure and whether the medicines are always being used appropriately. Yale Medicine says the most common side effects include nausea, vomiting, diarrhoea and constipation, while less common but more serious risks can include pancreatitis, gallbladder problems and allergic reactions. Other reviews have also raised concerns about possible kidney issues, thyroid-related risks and the effect of rapid weight loss on muscle and bone strength, although the strength of evidence varies by outcome.

One of the sharpest new concerns involves what happens when patients stop taking GLP-1 drugs. Axios reported that newer research is linking discontinuation to more than simple weight regain, including a higher risk of heart attack, stroke and death in some patients after treatment ends. The report cited a Washington University study that found a 22% higher risk of those outcomes over two years among patients who stopped therapy, while other studies have suggested rising blood sugar and a return of cardiovascular risk factors such as inflammation, high blood pressure and cholesterol.

Cost and access remain major barriers, and those pressures may be pushing some people towards unsafe alternatives. Almandoz said shortages, coverage gaps and high out-of-pocket prices can make it difficult for patients who would genuinely benefit to stay on treatment, while some estimates place monthly costs at roughly $700 to $800. Sarah Messiah, associate dean for research and director of the Child and Adolescent Population Health Programme at UT Southwestern, warned that this can encourage use of “grey market” products that are not approved by the Food and Drug Administration and may not be safe. Both experts stressed that GLP-1 medicines should be used with medical supervision and alongside diet and exercise changes, not as a standalone fix or a way to chase a lower number on the scales.