Anti-obesity drug users face significant weight rebound after stopping treatment
A comprehensive meta-analysis reveals that patients prescribed anti-obesity medications experience substantial weight regain starting eight weeks after discontinuing treatment, with the rebound effect continuing for an average of 20 weeks before stabilising. The research highlights critical challenges in long-term weight management strategies.
Patients who stop taking weight-loss medications may face an inevitable battle against returning weight, according to groundbreaking research published in BMC Medicine on 22 July 2025. The meta-analysis, conducted by researchers at Peking University People’s Hospital, examined data from 11 randomised trials involving 1,574 participants in treatment groups and 893 in control groups.
Weight regain trajectory emerges across multiple drug classes
The study analysed six FDA-approved anti-obesity medications (AOMs), including orlistat, phentermine-topiramate, and semaglutide, alongside glucagon-like peptide-1 (GLP-1) receptor agonists increasingly prescribed for weight management. Researchers tracked weight changes after patients discontinued their medications, controlling for factors including medication type, diabetes presence, and lifestyle interventions.
“Significant weight regain occurred 8 weeks after discontinuation of AOMs and was sustained through 20 weeks,” the authors concluded. “Different weight regain was observed in subjects with different characteristics.”
The trajectory of weight regain followed a consistent pattern across studies. At four weeks post-discontinuation, patients still maintained slight weight loss compared to control groups. However, by eight weeks, significant weight regain became evident, with patients gaining an average of 1.50 kg more than control groups. This upward trend continued, reaching 1.76 kg at 12 weeks and 2.50 kg at 20 weeks before plateauing.
GLP-1 medications show pronounced rebound effects
Subgroup analysis revealed particularly striking results for GLP-1 receptor agonists, which have gained prominence in weight management. At 12 weeks after discontinuation, only studies involving GLP-1-related drugs demonstrated significant weight regain compared to control groups.
The researchers noted that tirzepatide, a commercially available GLP-1 receptor agonist, exemplified this pattern. “Participants who completed a 36-week treatment of tirzepatide regained almost half the weight previously lost after switching to a placebo,” according to the study findings.
This pronounced rebound effect may relate to GLP-1’s mechanism of action. “GLP-1 can increase satiation and reduce appetite by binding to receptors in the central nervous system,” the authors explained. “In addition, GLP-1 causes delayed gastric emptying, which leads to weight loss.” When treatment stops, these appetite-suppressing and gastric-slowing effects diminish, leading to weight regain.
Lifestyle interventions show unexpected patterns
Contrary to conventional wisdom, the analysis revealed unexpected findings regarding lifestyle interventions. Patients who continued lifestyle modifications after stopping medication showed significant weight regain, whilst those without continued interventions did not demonstrate statistically significant rebound.
The researchers acknowledged this counterintuitive result may reflect limitations in the available data. “The specific pattern, intensity, and duration of lifestyle intervention in the included studies was not clear,” they noted, suggesting that incomplete information about intervention methods may have influenced these findings.
Clinical implications for long-term weight management
The study’s findings raise important questions about sustainable weight management strategies. The authors observed that “weight regain is common in various weight loss strategies,” noting that patients who received gastric bypass, vertical-banded gastroplasty, or gastric banding also regained more than 5% of their lowest weight at 15-year follow-up.
Xiaoling Cai and Linong Ji, the study’s corresponding authors, emphasised that their research excluded studies of lifestyle interventions and bariatric surgery, limiting direct comparisons between different weight-loss approaches. However, they noted that weight regain has been reported with other methods, including gastric bypass and vertical banded gastroplasty.
Mechanistic insights into weight cycling
The research team explored potential mechanisms underlying post-treatment weight regain, a phenomenon known as weight cycling. They cited evidence that “weight loss induces adverse gut hormonal changes that potentially affect weight regain and persist,” leading to increased hunger levels and eating urges that promote weight regain.
Additionally, weight loss associates with reduced resting energy expenditure due to changes in body composition – termed metabolic adaptation – which contributes to weight regain tendency.
Future research directions needed
The authors acknowledged several study limitations, including the small number of included trials and limited follow-up data at each time point. “Studies with longer follow-up duration are required to further investigate the potential factors associated with weight change after discontinuation of treatment,” they concluded.
The research underscores the complexity of obesity treatment and highlights the need for comprehensive, long-term approaches to weight management that extend beyond pharmaceutical interventions alone.
Reference
Wu, H., Yang, W., Guo, T., et. al. (22 July 2025). Trajectory of the body weight after drug discontinuation in the treatment of anti-obesity medications. BMC Medicine, 23, 398. https://doi.org/10.1186/s12916-025-04200-0
