Stopping weight loss drugs linked to weight regain and reversal of beneficial heart health markers

Stopping weight loss drugs is followed by weight regain and reversal of beneficial effects on heart and metabolic health markers such as high cholesterol and high blood pressure, according to a study by University of Oxford researchers.

The study shows that the average rate of weight regain is 0.4kg/month after stopping treatment, with weight and risk markers for diabetes and heart disease predicted to return to pre-treatment levels in less than two years. It also finds that the rate of weight regain after stopping weight loss drugs is almost four times faster than after diet and physical activity changes, irrespective of the amount of weight lost during treatment.

"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 stated.

The development of highly effective weight management medications such as glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide and tirzepatide, has transformed the treatment of obesity. Yet it is estimated that around half of people with obesity discontinue GLP-1 drugs within 12 months, so it's important to understand what happens to body weight and risk markers for conditions like diabetes and heart disease after stopping treatment.

To do this, a team of researchers from the University of Oxford searched registries and databases for trials and observational studies that compared the effects of any medication licensed for weight loss in adults with any non-drug weight loss intervention (behavioural weight management programs) or placebo. The studies were designed differently and varied in quality, but the researchers were able to assess their risk of bias using established tools.

Thirty-seven studies published up to February 2025, involving 9,341 participants, were included in the analysis. The average duration of weight loss treatment was 39 weeks, with an average follow-up of 32 weeks.

Participants treated with weight loss drugs regained on average 0.4 kg/month after stopping treatment and were projected to return to their pre-treatment weight by 1.7 years. All cardiometabolic risk markers were projected to return to pre-treatment levels within 1.4 years after stopping the drugs.

Monthly weight regain was also faster after weight loss drugs than after behavioural weight management programs (by 0.3 kg), independent of initial weight loss.

The authors acknowledge several limitations. For example, only eight studies assessed treatment with the newer GLP-1 drugs and the maximum follow-up period in these studies was 12 months after medication stopped. Moreover, few studies were at low risk of bias.

Nevertheless, the researchers point out that they used three methods of analysis and all provided similar results, adding certainty to their findings.

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

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