Cleveland Clinic study finds limited weight regain after stopping GLP-1 drugs

A real-world study of nearly 8,000 patients by Cleveland Clinic researchers shows that stopping injectable semaglutide or tirzepatide often does not lead to major weight regain. Many participants maintained or continued losing weight by restarting treatment, switching medications, or using lifestyle support. This differs from clinical trials where rapid regain was observed.

Researchers at Cleveland Clinic's Center for Value-Based Care Research analyzed outcomes for 7,938 adults with overweight, obesity, or type 2 diabetes in Ohio and Florida. All had started injectable semaglutide—sold as Ozempic or Wegovy—or tirzepatide—sold as Mounjaro or Zepbound—for obesity or diabetes, then discontinued within three to 12 months. The findings, published in Diabetes, Obesity and Metabolism (DOI: 10.1111/dom.70660), tracked weight changes over the following year and post-discontinuation strategies. Hamlet Gasoyan, DS, Ph.D., MPH, led the study. Patients treated for obesity lost an average of 8.4% body weight before stopping and regained just 0.5% after one year. Among them, 55% gained weight, while 45% maintained or kept losing. For type 2 diabetes patients, average loss was 4.4% pre-discontinuation, followed by an additional 1.3% loss. Here, 44% gained weight, and 56% maintained or lost more. Diabetes patients were more likely to restart due to better insurance coverage. Common reasons for stopping included cost or lack of insurance and side effects. Within a year, 27% switched medications, 20% restarted the original, 14% pursued lifestyle care with dietitians or exercise specialists, and less than 1% had bariatric surgery. '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,' Dr. Gasoyan said. He added, 'Many patients do not give up on their obesity treatment journey, even if they need to stop their initial medication.' The study underscores the role of flexible, ongoing care in clinical practice versus controlled trials.

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