Discontinuing GLP-1 Treatment Associated With Up to 60% Weight Regain, With Brajan Budini

After cessation of GLP-1 receptor agonist treatment, patients regain a substantial amount of the weight they lost while on medication, with 60% of weight regained after 1 year post-discontinuation.1

Despite their undeniable efficacy in reducing weight, GLP-1 RAs are not a permanent fix. Discontinuation of these medications has been proven to lead to substantial weight regain. Previous studies have indicated the degree to which weight can rebound after treatment discontinuation. However, the trajectory of this regain remains unknown, forestalling accurate estimates.2

“GLP-1 RAs really make use of the body's own system for regulating appetite, but what we're doing is they're acting more so as a brake on the appetite,” Brajan Budini, a medical student at the School of Clinical Medicine and Trinity College, University of Cambridge, told HCPLive in an exclusive interview. “Once you take your foot off that brake, you really do tend to regain weight quite rapidly. And this really goes to the point that these drugs aren't a magic fix.”

Budini and colleagues conducted a systematic search via MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science, identifying studies which tracked weight outcomes in patients after discontinuing GLP-1 therapy.1

Studies were included if they were randomized controlled trials (RCTs), non-randomized interventional studies, or observational studies reporting weight outcomes in adults with overweight or obesity, which was defined as a body mass index (BMI) ≥25 kg/m2 or ≥23 kg/m2 for specific populations. Additionally, studies had to have a treatment period of ≥8 weeks and a post-cessation follow-up of ≥4 weeks and could not include co-treatment with other weight loss drugs.1

The study’s primary outcome was percentage weight regain, defined as the percentage of weight regained after treatment discontinuation to the weight lost at the end of treatment. Budini and colleagues calculated this via end-of-treatment weight loss data and the weight reported at any time point following cessation. Secondary outcomes included changes in HbA1c and systolic blood pressure (SBP) following discontinuation.1

In total, 48 relevant studies were included, of which 36 were RCTs and 12 were non-randomized studies. Weight consistently rebounded after stopping GLP-1 treatment. 6 RCTs, comprising 3236 patients, were included in a nonlinear meta-regression, which utilized a mixed-effect exponential recovery model with random effects applied to the rate constant. After 1 year post-discontinuation, 60% of the weight lost during treatment was regained.1

After 52 weeks, investigators extrapolated weight trajectories, estimating a plateau in weight regain at 75.3% (95% CI, 68.9-81.6) of the weight lost at treatment. The rate constant was 0.0302 per week (95% CI, 0.0202-0.0401), which corresponds to a half-life of 23 weeks (95% CI, 17.3-34.3).1

Ultimately, Budini and colleagues declared these findings indicative of a need for re-evaluation of prescription guidelines, cessation strategies, and long-term support. They also encourage further research to analyze the makeup of the weight regained following cessation, given the potential loss of lean mass during GLP-1 treatment.1

“Although you do lose weight, it's also important thing about what you're losing, not just how much you're losing,” Budini said. “Of the weight that you're losing, 40% of that weight loss is lean mass, which is muscle mass. But what we were really interested in, and this hasn't again been answered, is, when you come off the drug and you regain the weight, what does the proportion of that regain look like? Are you regaining the same muscle and fat in the same ratio that you lost it? Or is the regain disproportionately fat?”

References

1. Budini B, Luo S, Tam M, et al. Trajectory of weight regain after cessation of GLP-1 receptor agonists: A systematic review and nonlinear meta-regression. eClinicalMedicine. Published online March 4, 2026:103796. doi:10.1016/j.eclinm.2026.103796

2. 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. doi:10.1136/bmj-2025-085304