What happens when patients stop taking GLP-1 medications? A new Cleveland Clinic study reveals real-world insights

As the use of injectable GLP-1 drugs continues to increase, questions persist about what happens after patients stop taking them in real-world settings.

A new Cleveland Clinic analysis of nearly 8,000 patients suggests that, on average, ceasing semaglutide and terzapatide does not lead to significant weight regain in clinical practice, as many patients later resume the original drug or try alternative obesity treatments.

In the largest real-world study to date examining obesity treatment use and long-term weight changes after GLP-1 discontinuation, Cleveland Clinic researchers found that most patients successfully stabilized their weight after one year through alternative therapies and therapeutic lifestyle interventions.

The findings, published in the journal Diabetes, Obesity and Metabolism, provide real-world context to previous randomized clinical trials that showed that patients who stopped taking semaglutide (sold under the names Ozempic/Wegovy) and tirzepatide (sold under the brand names Mounjaro/Zepbound) lost more weight over half a month.

Hamlet Gasoyan, DS, PhD, MPH, an investigator at the Cleveland Clinic’s Center for Value-Based Care Research, led the study.

“Our real-world data show that many patients who stop semaglutide or terzapatide restart the drug or switch to another obesity treatment, which may explain why they gain less weight than patients in randomized trials,” said Dr. Gaswan.

This cross-sectional study included 7,938 obese or overweight adults in Ohio and Florida. All patients started injectable semaglutide or terzapatide for obesity or type 2 diabetes and stopped the medication for three to 12 months. Dr. Gaswan and his research team analyzed which medications the patients followed and how their weight changed over time.

While patients in the study reported weight loss, individual results varied:

• Those treated for obesity lost an average of 8.4% of their body weight before stopping, and regained an average of 0.5% after one year.
• Those treated for type 2 diabetes lost an average of 4.4% of their body weight before stopping, and 1.3% of their body weight after one year.
• In the obese group, 55% gained weight in the year after stopping, while 45% lost or stayed the same.
• In the diabetic group, 44% gained weight, while 56% lost or stayed the same.

Research groups have previously documented two primary drivers that have contributed to patients stopping their medication: cost or insurance coverage limitations and side effects, with the former being the dominant reason. Those taking medication for diabetes were more likely to restart medication than those taking it for obesity, a difference linked to more consistent insurance coverage for diabetes-related prescriptions.

Overall, the majority of patients in both groups explored other weight management treatment options within 12 months of stopping their initial GLP-1 injection:

• 27% switched to a different drug (including older-generation obesity drugs or switching between semaglutide and terzapatide)
• 20% resumed their original medication
• 14% continued obesity treatment through lifestyle modification visits with health care professionals such as dietitians or exercise specialists.
• Less than 1% underwent metabolic and bariatric surgery.

Researchers say the findings highlight the importance of personalized, ongoing support for patients seeking obesity treatment — even when they stop medication.

“Many patients don’t give up on their obesity treatment journey, even if they need to stop their primary medications,” said Dr. Gasoyan. “In our future work, we will examine the comparative effectiveness of alternative treatment options for obesity in patients stopping semaglutide or terzapatide, to help patients and their clinicians make informed decisions.”