What happens to your weight after quitting GLP-1 anti-obesity drugs?

By Priyanjana Pramanik, MSc.Reviewed by Susha Cheriyedath, M.Sc.Jul 23 2025

A major meta-analysis finds that patients who discontinue anti-obesity medications quickly regain weight, yet, crucially, they still retain some of their original weight loss a year later, spotlighting the challenges and promise of long-term obesity treatment.

Review: Trajectory of the body weight after drug discontinuation in the treatment of anti-obesity medications. Image Credit: Caroline Ruda / Shutterstock

In a recent review article published in the journal BMC Medicine, researchers systematically reviewed and analyzed randomized controlled trials (RCTs) to assess the effect of discontinuing anti-obesity medications (AOMs) on long-term weight changes.

They concluded that significant weight regain began eight weeks after stopping AOMs and continued through 20 weeks, particularly for individuals who had previously taken glucagon-like peptide-1 (GLP-1) receptor agonists or those who had experienced greater weight loss during treatment or ongoing lifestyle interventions. However, in several subgroup analyses, some differences—such as between those with greater versus lesser initial weight loss—were not statistically significant by week 12.

Concerns about discontinuing AOMs

Obesity, affecting over 2.2 billion adults globally in 2020 and projected to rise to 3.3 billion by 2035, is linked to significant health risks, including some cancers, cardiovascular disease, and type 2 diabetes.

Treatment typically involves lifestyle changes, medications, and bariatric surgery. Among these, AOMs have shown success in promoting weight loss and improving related health outcomes.

However, concerns remain about weight regain after stopping AOMs. Studies have shown that discontinuation of drugs like semaglutide and orlistat often leads to significant weight regain and worsening of metabolic measures, such as blood sugar and blood pressure. Additionally, some studies report that metabolic indicators such as plasma lipids and insulin concentrations may also revert after weight regain.

Yet, most prior research on weight regain has focused on surgical or behavioral interventions, leaving a gap in understanding the effects of stopping pharmacological treatments.

About the review

This meta-analysis was designed to address that gap by systematically evaluating the long-term effects of AOMs after treatment cessation, particularly the trajectory of weight changes in the weeks and months that follow.

The authors analyzed data from 11 randomized controlled trials involving 2,466 participants (1,573 in the treatment group and 893 in the control group), all of which reported weight data both during and after treatment.

The review covered a range of medications, including six trials on GLP-1 receptor agonists, one on dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, one on orlistat, two on phentermine-topiramate, and one on naltrexone-bupropion.

Eight studies used placebo controls and three used active drug controls. All studies were judged to have low risk of bias.

Weight regain patterns after AOM discontinuation

Weight regain became noticeable about eight weeks after stopping AOMs, increasing until around week 20 before stabilizing. No significant difference was observed at four weeks; however, from eight weeks onward, those who had used AOMs regained significantly more weight than the controls.

The amount of average weight regain was 1.5 kg at 8 weeks, 1.76 kg at 12 weeks, 2.5 kg at 20 weeks, 2.3 kg at 26 weeks, and 2.47 kg at 52 weeks. Despite this regain, participants who had used AOMs still maintained a net weight loss compared to their pre-treatment baseline at 52 weeks, indicating a lasting benefit even after discontinuation of the medication.

When grouped by initial weight, both lower- and higher-weight subgroups showed significant weight regain, with no meaningful difference between them. Body mass index (BMI)-based subgroup analysis revealed significant regain only in those with a BMI below 35, which was unexpected.

BMI trajectory followed a similar pattern to weight, with increases observed from week 10 onward. At 26 and 52 weeks, BMI gains were 0.70 and 0.82 kg/m², respectively.

Meta-regression analysis found that baseline BMI, health status, sex, and age did not significantly influence the extent of weight regain. Similarly, control type, treatment duration, follow-up time, and weight loss rate were not found to be associated with differences in post-treatment weight regain.

Other influencing factors

Significant weight regains occurred in both placebo-controlled and actively controlled trials, with no meaningful difference between them. When comparing participants with obesity alone versus those with obesity and type 2 diabetes, both groups showed significant regain, again with no significant difference.

Participants who had used GLP-1-based therapies experienced significant weight regain. In contrast, non-GLP-1-based drug studies did not show statistically significant weight regain. However, the difference in weight regain between GLP-1 and non-GLP-1 groups was also not statistically significant.

Interestingly, trials that continued lifestyle interventions such as exercise and diet after stopping AOMs still showed significant weight regain (1.83 kg). In contrast, studies without continued behavioral support did not show substantial regain, though this finding was based on limited data and should be interpreted cautiously. The authors note that these results contrast with previous research supporting the value of ongoing lifestyle intervention, and suggest that limited sample sizes, intervention heterogeneity, or study designs may have contributed to this unexpected finding.

Participants who experienced greater weight loss during treatment were more likely to regain weight after stopping medication. However, by 12 weeks post-treatment, the difference in regain between those with larger versus smaller initial losses was not statistically significant. Similarly, fast and slow weight loss subgroups both experienced comparable levels of regain.

Adverse events were reported in a subset of studies, but there was insufficient evidence to determine any association between adverse events during treatment and subsequent weight regain.

Conclusions

This meta-analysis found that stopping AOMs often leads to significant weight regain, which begins around eight weeks and stabilizes by six months. This pattern is similar to rebound effects seen after bariatric surgery or behavioral weight loss.

Weight regain occurred across different subgroups, including those with varying health conditions, baseline weights, and BMIs, and was more pronounced in individuals who lost more weight during treatment. However, many subgroup differences were not statistically significant, and results should be interpreted with caution given the limited number of included studies for several analyses.

GLP-1-based therapies showed a notable rebound, likely due to the loss of metabolic and appetite-suppressing effects after treatment cessation. Behavioral and biological mechanisms, such as psychological factors and hormonal shifts, may contribute, but remain poorly understood. Lifestyle interventions did not prevent regain, contrasting with prior evidence, though limited data and variability between studies may explain this discrepancy.

Key limitations include a small number of studies, variation in design, and a lack of focus on post-treatment outcomes in some trials. The analysis was also primarily limited to weight and BMI outcomes, and potential heterogeneity due to different AOM classes and study durations may influence the results. More long-term studies are needed to better understand weight regain and improve obesity treatment strategies.