Study raises concerns over long-term effectiveness of GLP-1s

Researchers have found that people regain weight faster after quitting these GLP-1s  compared with after diet and exercise alone. Improvements in heart health and diabetes risk also tend to reverse within a few years. The results suggest long-term success may require more than medication alone. The findings call into question how durable these treatments really are.

On average, individuals regained about 0.4 kilograms per month after stopping medication. Based on these trends, body weight and key risk markers for diabetes and heart disease were projected to return to pre-treatment levels in under two years.

The study also found that weight regain after stopping medication happened much faster than after weight loss achieved through diet and physical activity. In fact, the pace of regain was nearly four times higher, regardless of how much weight a person 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 researchers write.

Newer weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide (Ozempic, Wegovy, and Rybelsus) and tirzepatide (Mounjaro and Zepbound), have significantly reshaped obesity treatment by helping many patients lose substantial amounts of weight.

However, about half of people with obesity stop using GLP-1 drugs within a year. That high discontinuation rate makes it especially important to understand what happens to weight and health risks related to diabetes and heart disease once treatment is discontinued.

To examine these outcomes, researchers from the University of Oxford reviewed clinical trials and observational studies involving adults who used medications approved for weight loss. These results were compared with outcomes from non-drug approaches such as behavioural weight management programs or placebo treatments.

Although the included studies varied in design and quality, the research team evaluated potential bias using established assessment tools to ensure consistency across the analysis.

In total, 37 studies published through February 2025 were included, covering 9,341 participants. On average, people received weight loss treatment for 39 weeks and were followed for about 32 weeks afterward.

Across the studies, participants who stopped taking weight loss drugs regained an average of 0.4 kilograms per month. Based on this rate, researchers estimated that body weight would return to pre-treatment levels within about 1.7 years.

Cardiometabolic risk markers showed a similar pattern. Measures related to heart disease and metabolic health were projected to return to baseline within roughly 1.4 years after medication was discontinued.

Weight regain was also consistently faster following drug-based weight loss than after behavioural weight management programs, with an average difference of 0.3 kilograms per month. This pattern held true regardless of how much weight was lost during treatment.

However, the authors note several limitations. Only eight of the included studies examined newer GLP-1 medications, and none followed participants for more than 12 months after stopping treatment. In addition, relatively few studies were rated as having a low risk of bias.

Nevertheless, the researchers emphasize that they used three different analytical approaches, all of which produced similar results.

"This evidence cautions against short term use of weight management medications, emphasizes the need for further research into cost effective strategies for long term weight control, and reinforces the importance of primary prevention,” they concluded.

The findings were reported in the paper, ‘Weight regain after cessation of medication for weight management: systematic review and meta-analysis’, published in the BMJ. To access this paper, please click here