Discontinuing semaglutide and tirzepatide, on average, does not lead to significant weight regain

A Cleveland Clinic analysis of nearly 8,000 patients suggests that discontinuing semaglutide and tirzepatide, on average, does not lead to significant weight regain in clinical practice, as many patients later restart the original medication or try an alternative obesity treatment.

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

The findings provide real-world context to previous randomized clinical trials indicating that patients who stopped semaglutide (sold under the brand names Ozempic/Wegovy) and tirzepatide (sold under the brand names Mounjaro/Zepbound) regained more than half of the weight they lost within 12 months.

"Our real-world data show that many patients who stop semaglutide or tirzepatide restart the medication or transition to another obesity treatment, which may explain why they regain less weight than patients in randomized trials," said Dr Hamlet Gasoyan, a researcher with Cleveland Clinic's Center for Value-Based Care Research, led the study.

This retrospective cohort study included 7,938 adult patients with obesity or overweight in Ohio and Florida. All patients initiated injectable semaglutide or tirzepatide for obesity or type 2 diabetes and stopped the medication within three to 12 months. Dr. Gasoyan and his research team analysed what treatments patients pursued next and how their weight changed over time.

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

• Those treated for obesity lost an average of 8.4% of body weight before discontinuation, and regained an average of 0.5% one year later.

• Those treated for type 2 diabetes lost an average of 4.4% of body weight before discontinuation, and lost an additional 1.3% of body weight one year later.

• In the obesity group, 55% gained weight in the year after discontinuation, while 45% kept losing or stayed the same.

• In the diabetes group, 44% gained weight, while 56% kept losing or stayed the same.

The research group earlier documented two primary drivers that contributed to patients stopping their medication: cost or insurance coverage limitations and side effects, with the former being the dominant reason.

Individuals taking the drugs for diabetes were more likely to restart the medication compared with those using them for obesity, a difference associated with more consistent insurance coverage for diabetes-related prescriptions.

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

• 27% switched to a different medication (including older-generation obesity medications or switching between semaglutide and tirzepatide)

• 20% restarted their original medication

• 14% continued their obesity treatment via lifestyle modification visits with health care professionals such as dietitians or exercise specialists.

• Less than 1% transitioned to undergoing metabolic and bariatric surgery.

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

"Many patients do not give up on their obesity treatment journey, even if they need to stop their initial medication," added Gasoyan. "In our future work, we will examine the comparative effectiveness of alternative treatment options for obesity in patients who discontinue semaglutide or tirzepatide, to help patients and their clinicians make informed decisions."

The findings were reported in the paper, ‘Obesity Treatments and Weight Changes in Clinical Practice After Discontinuation of Semaglutide or Tirzepatide’, published in Diabetes, Obesity and Metabolism. To access this paper, please click here