Anti-obesity medications associated with weight rebound post-treatment,suggests study

Patients prescribed drugs to help them lose weight may experience a rebound in weight gain after halting their prescription, finds a meta-analysis published in BMC Medicine. The study, which analyses data for patients receiving weight loss drugs across 11 randomised trials, suggests that while the amount of weight regain varies depending on the specific drug, there is a broad trend in associated weight regain after the course of medication concluded.

Six anti-obesity medications (AOMs) have been approved by the US FDA for use in assisting with weight loss, including orlistat, phentermine-topiramate, and semaglutide. Glucagon-like peptide-1 (GLP-1) — a therapeutic developed to assist with diabetes-has also increasingly been prescribed to help patients lose weight. However, recent studies have suggested that patients prescribed AOMs may regain weight in the months after stopping taking these medications.

Xiaoling Cai, Linong Ji, and colleagues conducted a meta-analysis of 11 studies from around the world investigating weight change in patients after they stopped taking AOMs. Overall, the authors analysed data from 1,574 participants in treatment groups and 893 in control groups. Weight change was measured by changes in body weight and BMI after stopping medication. Of the 11 studies included in the meta-analysis: six focused on GLP-1 receptor agonists (RAs); one focused on GLP-1 and GLP dual Ras; one study focused on orlistat; two studies on phentermine-topiramate; and one study on naltexone-bupriopion.

The authors controlled for different contributing factors, including medication type, the presence of diabetes, and the presence or absence of lifestyle changes like diet or exercise. Their analysis found that AOMs were associated with significant weight loss while being used, followed by weight regain starting eight weeks after AOM discontinuation, with weight regain then continuing for an average of 20 weeks before plateauing. Weight regain varied with follow-up, with study participants experiencing significant periods of weight regain at eight, 12, and 20 weeks after AOM discontinuation. The amount of weight regained depended on several factors, including the type of medication taken by participants and the consistency of their lifestyle change. For example, participants who completed a 36-week treatment of tirzepatide, a commercially available GLP-1 RA, regained almost half the weight previously lost after switching to a placebo.

The authors note the meta-analysis did not include studies of lifestyle interventions and bariatric surgery, reducing the degree to which different weight loss approaches could be compared within the context of the study. They also note that weight regain has been reported with other weight loss methods, such as gastric bypass and vertical banded gastroplasty.

Reference:

Wu, H., Yang, W., Guo, T. et al. Trajectory of the body weight after drug discontinuation in the treatment of anti-obesity medications. BMC Med 23, 398 (2025). https://doi.org/10.1186/s12916-025-04200-0.