Stopping popular weight-loss injections like Ozempic or Mounjaro might not trigger the dramatic kilogram-laden rebound many fear, according to a study of nearly 8 000 patients.
The research found that most people who discontinue these drugs manage to keep the weight off – or even continue losing – by restarting treatment, switching medications, or adopting lifestyle changes, with the study team from Cleveland Clinic saying that while earlier clinical trials suggested rapid weight regain, their large real-world analysis paints a more hopeful picture.
This was one of the largest real-world studies so far to examine long-term outcomes after discontinuing GLP-1 therapies.
Real-world data vs clinical trial results
The findings, published in Diabetes, Obesity and Metabolism, offer important context to earlier randomised clinical trials.
Those trials showed 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 had lost within a year.
The new data suggest that outcomes may differ in everyday clinical practice, where patients have more flexibility to adjust their treatment plans.
Hamlet Gasoyan, DS, PhD, MPH, a researcher with Cleveland Clinic's Centre for Value-Based Care Research, led the study.
“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 randomised trials," Gasoyan said.
Patient outcomes
The retrospective cohort study included 7 938 overweight or obese adults, all of whom began treatment with injectable semaglutide or tirzepatide for either obesity or type 2 diabetes, then stopped using the medication within three to 12 months.
Researchers tracked what treatments patients pursued afterward and how their weight changed over time.
Although most of them experienced meaningful weight loss, results varied:
• Patients treated for obesity lost an average of 8.4% of their body weight before stopping the medication, and regained an average of 0.5% after one year.
• Patients treated for type 2 diabetes lost an average of 4.4% before discontinuation and went on to lose an additional 1.3% over the next year.
• Among those treated for obesity, 55% gained weight after stopping, while 45% either continued losing weight or maintained their weight.
• In the diabetes group, 44% gained weight, while 56% maintained or continued to lose weight.
Why patients stop
Previous research by the same team identified two main reasons patients stop taking these medications: cost or lack of insurance coverage, and side effects.
Financial barriers were the most common factor. Patients using the drugs for type 2 diabetes were more likely to restart treatment compared with those using them for obesity. This difference appears to be linked to more consistent insurance coverage for diabetes prescriptions.
Within a year of stopping their initial GLP-1 medication, many patients explored other weight management strategies:
• 27% switched to another medication (including older-generation obesity drugs or switching between semaglutide and tirzepatide)
• 20% restarted their original medication
• 14% continued treatment through lifestyle-focused care with professionals like dieticians or exercise specialists
• Less than 1% underwent metabolic and bariatric surgery
Ongoing support key
Researchers say these findings highlight the importance of continued, individualised care for people managing obesity, even if they stop medication.
“Many patients do not give up on their obesity treatment journey, even if they need to stop their initial medication," said 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."
Study details
Obesity Treatments and Weight Changes in Clinical Practice After Discontinuation of Semaglutide or Tirzepatide
Hamlet Gasoyan, Rebecca Schulte, Christopher Boyer, et al.
Published in Diabetes, Obesity and Metabolism on 12 March 2026
Abstract
Aims
To describe obesity treatments in real-world settings after discontinuation of semaglutide or tirzepatide and variability in weight change post-discontinuation.
Materials and Methods
This retrospective cohort study used electronic health records from 1 January 2021, to 30 June 2025, in a large health system in Ohio and Florida. Adults with overweight or obesity who initiated injectable semaglutide or tirzepatide for obesity or T2D between 2021 and 2023 and discontinued the medication within 3–12 months were included. Main outcomes were re-initiation of the index medication or receipt of an alternative treatment, body weight changes from baseline to index medication discontinuation and from discontinuation to one-year post discontinuation.
Results
A total of 7 938 patients (mean [SD] age, 55.7 [13.4] years; 5061 [63.8%] female) were identified. During 1-year post-discontinuation, 19.6% restarted the index medication and 35.2% received an alternative obesity treatment, including starting another medication (27.4%), lifestyle modification visit (13.7%) and metabolic and bariatric surgery (0.6%). Mean percentage weight change from baseline to discontinuation was −8.4% [95% CI, −8.7%, −8.1%] when treating obesity and −4.4% [95% CI, −4.7%, −4.2%] when treating T2D. Mean percentage weight change from discontinuation to 1 year later was 0.5% [95% CI, 0.0%, 1.0%] when treating obesity and −1.3% [95% CI, −1.6%, −1.0%] when treating T2D; however, there was considerable individual-level variability.
Conclusion
In this large sample of patients who discontinued semaglutide or tirzepatide, reinitiation of the original medication or receipt of alternative obesity treatment was common. The average weight change one-year post-discontinuation was relatively small; however, there was considerable individual-level variability.
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