A new analysis from Cleveland Clinic, involving nearly 8,000 patients, suggests that stopping drugs like semaglutide and tirzepatide does not typically result in major weight regain in real-world settings. Many patients either restart treatment later or switch to other weight management options, which may help limit weight gain.

In one of the largest real-world studies so far to examine long-term outcomes after discontinuing GLP-1 therapies, researchers found that a significant number of patients were able to maintain stable weight over a year. This was often achieved through alternative treatments and structured lifestyle support.

Real-World Data vs Clinical Trial Results

The findings, published in the journal Diabetes, Obesity and Metabolism, offer important context to earlier randomized 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, Ph.D., MPH, a researcher with Cleveland Clinic's Center 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 randomized trials," Dr. Gasoyan said.

Study Details and Patient Outcomes

This retrospective cohort study included 7,938 adults with overweight or obesity in Ohio and Florida. All participants 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 participants experienced meaningful weight loss, results varied across individuals:

• 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 following 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 and What They Do Next

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 such as dietitians or exercise specialists
• Less than 1% underwent metabolic and bariatric surgery

Ongoing Support Key to Long-Term Weight Management

Researchers say these findings highlight the importance of continued, individualized 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 Dr. 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."