Obesity is a chronic, complex, and relapsing disease affecting approximately two billion adults globally and is associated with an increased risk of premature morbidity and mortality. Behavioural weight management programmes (BWMPs) are the main treatments for weight loss. But newer weight management medications (WMMs) like dual glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) agonists and GLP-1 agonists can achieve 15-20% of weight loss with cardiometabolic benefits. However, real-world studies demonstrate that approximately half of the users discontinue these drugs within one year, often leading to weight regain. Hence, understanding what happens after cessation of treatment is clinically important. A recent systematic review published in BMJ aimed to quantify weight regain and changes in cardiometabolic health after stopping WMMs, with a particular focus on newer incretin-based therapies, and to compare these outcomes with those observed following BWMPs.
This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and were registered with the International Prospective Register of Systematic Reviews (PROSPERO). Searches for trial registries and different databases such as Web of Science, CINAHL, Embase, PsycINFO, and Medline were searched from inception to February 2025. Observational studies, randomized controlled trials (RCTs), and non-randomized trials involving adults with obesity or overweight were eligible. Included studies evaluated WMMs use for ≥8 weeks with ≥4 weeks follow-up after stopping the treatment, with comparators of non-drug interventions or placebo. Cardiometabolic changes and weight regain were analyzed through time-to-event analysis, mixed models, and meta-regression, with formal assessment of bias risk and certainty of evidence.  The primary endpoint was the rate of weight gain after treatment stopped, and the secondary endpoints were changes in cardiometabolic markers.
A total of 37 studies were included, comprising 63 intervention arms and 9,341 participants. Of these, 35 were RCTs, but only 28 RCTs had control groups. The mean treatment duration was found to be 39 weeks (range = 11 to 176) with a mean follow-up of 32 weeks (4 to 104). Across all WMMs, mean weight loss at treatment cessation was 8.3 kg (95% confidence interval [CI]: 7.2-9.5). Mixed-effects model analysis revealed an average rate of weight regain after stopping WMMs was 0.4 kg/month (95% CI: 0.3-0.5). Weight regain occurred more rapidly with incretin-based therapies at 0.5 kg/month (95% CI: 0.4-0.7) for all incretin mimetics and 0.8 kg/month (95% CI: 0.7-0.9) for newer, more effective agents (tirzepatide and semeglutide). This corresponded to an estimated weight regain within the first year of 4.8 kg, 6 kg, and 9.9 kg, respectively.
In RCTs, after cessation, the monthly rate of weight regain was significantly faster compared to control by 0.3 kg for all WMMs, 0.6 kg for incretin mimetics, and 0.8 kg for newer incretin agents, with all P <0.001. Time-to-event analysis estimated that there was no significant difference between intervention and control groups after 1.1-1.4 years.
Cardiometabolic benefits also diminished following treatment cessation. HbAIc decreased by 0.9 mmol/mol (95% CI: 0.5-1.3) during treatment but rose by 0.05 mmol/mol per month (95% CI: 0.03-0.08) after cessation, returning to baseline within 1.4 years. Compared with BWMPs, WMMs produced greater initial weight loss (mean difference: 3.2 kg); however, weight regain occurred more rapidly, at an additional 0.3 kg/month. Weight was predicted to return to baseline after 1.7 years following WMM cessation, compared with 3.9 years after BWMPs. Overall, the certainty of evidence for weight regain was rated as moderate.
This study’s limitations included limited long-term follow-up data for newer incretin-based drugs, dependence on projected and linear regression model analysis, indirect comparisons with BWMPs, heterogeneity in study populations, and a low risk of bias in only a few studies.
In conclusion, this review suggests that WMMs decrease weight and improve cardiometabolic health, but benefits fade within 1.7 years after stopping. These findings underscore the need for cost-effective, sustainable, and long-term strategies for weight management and obesity prevention.
Reference: West S, Scragg J, Aveyard P, et al. Weight regain after cessation of medication for weight management: systematic review and meta-analysis. BMJ. 2026;392:e085304. doi:10.1136/bmj-2025-085304
