Many Patients Stop GLP-1s Before Reaching Target Dose: Hamlet Gasoyan, PhD

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Patients who stop taking glucagon-like peptide-1 (GLP-1) receptor agonists for obesity treatment often do so before reaching effective maintenance dosages, which may limit the drug’s potential for weight loss and increase the likelihood of suboptimal outcomes, according to Hamlet Gasoyan, PhD, researcher at the Center for Value-Based Care Research at Cleveland Clinic.

In an interview with The American Journal of Managed Care^® (AJMC^®), Gasoyan expanded on findings from a Cleveland Clinic study that showed real-world use of GLP-1s semaglutide and tirzepatide yields less weight loss than randomized trials, primarily due to early discontinuation and low maintenance dosing.¹ He explained that since GLP-1 medications require slow titration, patients who stop within the first few months often haven’t even reached the recommended dose of 2.4 mg.

“Those who discontinue in the first few months, they don't ever get a chance to reach that high maintenance dosage,” Gasoyan told AJMC. “There is the component where patients who discontinue early for a variety of reasons never achieve the high maintenance dosage, and that's incorporated in the overall rate of low maintenance dosages used in our overall study cohort.”

While the study did not specifically assess whether lower dosages contributed to discontinuation, Gasoyan noted this is a question worth looking at in further research. What is more evident is that many patients stop treatment by month 1 before titrating up to the optimal dose, which takes around 4 months.^2,3 The patient-provider relationship plays a critical role in whether a patient remains on treatment long enough to benefit from it, explained Gasoyan, who said initiating discussions early about costs, potential adverse effects, and what to expect with dose escalation may improve adherence and reduce early dropout.

For obesity management, he said patients often see their providers every 3 months or so, but the conversation is ongoing between visits. While some patients may not see their provider in person by the time they stop GLP-1 therapy, there are opportunities outside of those visits to talk about concerns and possible discontinuation.

“What our study adds is real-world data, because each provider only knows about their patients, or each patient knows about their case,” Gasoyan told AJMC. “Reporting on how common this is in terms of discontinuation of lower maintenance dosages, this will be an important topic to get started right at the beginning of the treatment.”

Gasoyan also warned that short courses of treatment offer low-value care for both patients and the health care system. These medications are costly, and when not used long enough to drive significant weight loss or metabolic benefit, the return on investment drops sharply.

The Cleveland Clinic research team is currently analyzing more granular data on why patients discontinue therapy. While they did not directly measure the relationship between dose and adverse effects, Gasoyan noted an anecdotal trend: higher doses may bring greater efficacy but also more side effects.

“This also coincides with the latest randomized controlled trial from very-high-dose semaglutide…way above 2.4 [mg]…. But this is something that we would like to study further to have more evidence-based data,” he said.

References

1. Klein HE. Real-world use of GLP-1s yields less weight loss than clinical trials. AJMC^®. June 10, 2025. Accessed June 17, 2025. https://www.ajmc.com/view/real-world-use-of-glp-1s-yields-less-weight-loss-than-clinical-trials

2. Klein HE, Gasoyan H. Cost and coverage issues drive GLP-1 discontinuation: Hamlet Gasoyan, PhD. AJMC. June 17, 2025. Accessed June 17, 2025. https://www.ajmc.com/view/cost-and-coverage-issues-drive-glp-1-discontinuation-hamlet-gasoyan-phd

3. Melillo G. Trial finds semaglutide with lifestyle intervention reduces body weight by nearly 15%. AJMC. February 10, 2021. Accessed June 17, 2025. https://www.ajmc.com/view/trial-finds-semaglutide-with-lifestyle-intervention-reduces-body-weight-by-nearly-15-