Weight Regain After GLP-1 Discontinuation is Less Rapid in Real World: Hamlet Gasoyan, PhD

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In real-world settings, patients who stop taking glucagon-like peptide-1 (GLP-1) receptor agonists to treat obesity may not experience the rapid weight regain commonly observed in clinical trials, according to Hamlet Gasoyan, PhD, a researcher at the Center for Value-Based Care Research at Cleveland Clinic.

Continuing the conversation around his team’s latest study, Gasoyan told The American Journal of Managed Care® (AJMC®), that one of the more surprising findings was that many patients who stopped semaglutide or tirzepatide in Ohio and Florida did not regain significant weight over the next several months, straying from clinical trial outcomes.1

“There have been 2 major clinical trials where either semaglutide was stopped or tirzepatide was stopped, and in both trials, patients did regain most of their weight that they lost during the leading period,” he explained, citing the STEP 1 (NCT03548935) and SURMOUNT-4 (NCT04660643) trials.2,3 Meanwhile, real-world data showed more stable weight trajectories.1

Gasoyan offered 2 main reasons for this discrepancy. First, patients in trials typically lose more weight due to longer treatment duration, so discontinuation leads to a sharper rebound. In the Cleveland Clinic cohort, patients who discontinued therapy had smaller weight losses to begin with, making it easier to maintain. Second, unlike trials where treatment is abruptly withdrawn, patients in real-world care often continue to pursue weight management through other means. This could include switching to older antiobesity medications, pausing and resuming GLP-1 therapy later, or engaging in lifestyle-based approaches like diet changes.

“Even after discontinuation of GLP-1s for 3 months or so, patients’ journeys in treating their obesity does not stop, which is an encouraging thing to us, and also gives us a task to produce evidence-based recommendations for them in terms of what's next,” Gasoyan told AJMC.

References

1. Klein HE. Real-world use of GLP-1s yields less weight loss than clinical trials. AJMC®. June 10, 2025. Accessed June 16, 2025. https://www.ajmc.com/view/real-world-use-of-glp-1s-yields-less-weight-loss-than-clinical-trials
2. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725
3. Aronne LJ, Sattar N, Horn DB, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48. doi:10.1001/jama.2023.24945