Cost and Coverage Issues Drive GLP-1 Discontinuation: Hamlet Gasoyan, PhD

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In real-world practice, patients taking glucagon-like peptide-1 (GLP-1) receptor agonists as an obesity treatment experience less weight loss than those in clinical trials, according research from Cleveland Clinic. Hamlet Gasoyan, PhD, researcher for the Center for Value-Based Care Research at Cleveland Clinic, expanded on these findings in an interview with The American Journal of Managed Care^®(AJMC^®), adding that a follow-up study currently under peer review identified top reasons for discontinuation.

Nearly half of the patients discontinued therapy due to high costs or insurance-related barriers, according to Gasoyan, with adverse effects and drug shortages also being factors. Patients often encounter issues with prior authorizations after the first fill or lose access to manufacturer co-pay coupons, making continued therapy financially unsustainable.

“For example, a patient could have started on the medication, the first fill would be done at the pharmacy, and then for the second fill, their insurance preauthorization wouldn't go through,” he told AJMC. Patients could also be using a manufacturer discount coupon the first month that expires the second, he said, leaving them with higher out-of-pocket costs than expected and creating a new barrier for that patient. In other cases, patients start off paying out of pocket, but stop when it becomes too expensive for them.

Although the study did not aim to directly compare tirzepatide against semaglutide, the findings mirrored randomized controlled trial data showing greater efficacy for tirzepatide. Gasoyan noted the patients who started tirzepatide were slightly younger, but otherwise the clinical and demographic profiles were comparable between treatment arms.

The Cleveland Clinic study included 7881 adults with obesity and showed that, while GLP-1 receptor agonists like semaglutide and tirzepatide can support meaningful weight loss in patients with prediabetes, real-world outcomes were weaker than those seen in randomized trials.

According to the study, patients who maintained GLP-1 therapy for a year lost 11.9% of their body weight on average. However, patients who discontinued treatment within 3 months only lost 3.6% on average while those who discontinued between 3 and 12 months of treatment lost 6.8%. Researchers also found that patients on high maintenance doses lost the most weight, with an average weight loss of 13.7% with semaglutide and 18.0% with tirzepatide.

Reference

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