Medications such as GLP-1 receptor agonists have changed how obesity and weight-related conditions are treated, producing substantial weight loss and improvements in blood pressure, cholesterol and blood sugar for many people. But new research suggests those benefits often fade once treatment stops.
In a systematic review and meta-analysis published in The BMJ, researchers analyzed what happens to body weight and cardiometabolic health after people discontinue prescription weight-loss medications. Across dozens of studies, they found that weight regain is common and that improvements in markers linked to heart disease and diabetes tend to reverse alongside it.
The analysis included 37 randomized trials and observational studies involving more than 9,300 adults. On average, participants regained about 0.4 kilograms per month after stopping medication. Based on these trajectories, body weight and cardiometabolic risk markers were projected to return to pre-treatment levels in under two years.
The review also found that weight regain occurred faster after stopping weight-loss medications than after stopping behavioral weight-management programs focused on diet and physical activity, regardless of how much weight participants had initially lost.
“This evidence suggests that despite their success in achieving initial weight loss, these drugs alone may not be sufficient for long term weight control,” the study authors wrote.
Many of the medications included in the review act on appetite and satiety pathways, including newer GLP-1 receptor agonists such as semaglutide and tirzepatide. While these drugs can produce significant weight loss during treatment, previous research has shown that a large share of users discontinue them within the first year, often due to cost, side effects or access issues.
The authors emphasized that weight regain after stopping medication reflects underlying biology rather than individual failure. When treatment ends, the physiological systems that regulate appetite, energy expenditure and fat storage tend to reassert themselves, driving weight back toward its previous level.
The researchers acknowledged several limitations. Only a small number of studies included the newest GLP-1 medications, and follow-up after stopping treatment was often limited to 12 months. Many studies were also at moderate or high risk of bias. Still, three different analytical approaches produced similar results, increasing confidence in the overall findings.
In an accompanying editorial, an independent researcher cautioned against viewing GLP-1 drugs as a permanent solution.
“People taking GLP-1 receptor agonists should be aware of the high discontinuation rate and the consequences of cessation of medications,” he wrote, adding that dietary and lifestyle practices remain important components of long-term weight management.
The findings do not suggest that weight-loss medications are ineffective or inappropriate. Instead, they underscore the chronic nature of obesity and the challenge of maintaining weight loss over time. The authors concluded that more research is needed to identify cost-effective, sustainable strategies for long-term weight regulation, including how medications might be combined with ongoing lifestyle and clinical support.
The study was funded in part by the National Institute for Health and Care Research (NIHR) and related UK biomedical research centers, with additional support from public research foundations. Some authors reported research support from public agencies and foundations.