Patients who discontinue glucagon-like peptide-1 (GLP-1) receptor agonists for obesity treatment may not experience the rapid weight regain typically seen in clinical trials, according to Hamlet gasoyan, PhD, a researcher at the Center for Value-Based care Research at Cleveland Clinic.

Following up on his team’s recent study,Gasoyan noted that a surprising finding was that many patients in Ohio and Florida who stopped semaglutide or tirzepatide did not regain important weight over several months,differing from clinical trial results.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, referencing the STEP 1 (NCT03548935) and SURMOUNT-4 (NCT04660643) trials.^2,3 Though, real-world data indicated more stable weight patterns.¹

Gasoyan suggested two primary reasons for this difference. First, clinical trial participants often experience greater initial weight loss due to longer treatment durations, leading to a more pronounced rebound upon discontinuation. In the cleveland clinic cohort, patients who stopped therapy had more modest initial weight losses, making maintenance easier. Second, unlike the abrupt cessation in trials, real-world patients often pursue ongoing weight management through alternative strategies, such as switching to older medications, pausing and resuming GLP-1 therapy, or adopting lifestyle changes like dietary adjustments.

“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 said.

real-World vs. Clinical Trial Outcomes