As injectable GLP-1 drugs become more widely used, many people are wondering what happens if patients stop taking injectable GLP-1 drugs outside of controlled clinical trials.
A new Cleveland Clinic analysis of about 8,000 patients suggests that stopping drugs such as semaglutide and tirzepatide usually does not result in significant weight gain in the real world. Many patients later either restart treatment or switch to other weight management options to help limit weight gain.
In one of the largest real-world studies to date examining long-term outcomes after discontinuing GLP-1 therapy, 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 systematic lifestyle support.
Real-world data and clinical trial results
The survey results were published in a magazine diabetes, obesity, metabolismprovides important context for early randomized clinical trials. These trials showed that patients who stopped taking semaglutide (sold under the brand name Ozempic/Wegovy) and tirzepatide (brand name Mounjaro/Zepbound) regained more than half of the weight they lost within a year.
New data suggest that results may be different in daily clinical practice, where patients have more flexibility to adjust their treatment plans.
Hamlet Gasoyan, MD, MPH, a researcher at Cleveland Clinic’s Value-Based Care Research Center, led the study.
“Our real-world data show that many patients who discontinue semaglutide or tirzepatide either restart the medication or move on 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 overweight or obese adults from Ohio and Florida. All participants started treatment with semaglutide or tirzepatide injections for either obesity or type 2 diabetes and then stopped using the drugs within 3 to 12 months. The researchers tracked what treatments the patients received and how their weight changed over time.
Most participants experienced significant weight loss, but results varied between individuals.
- Patients treated for obesity lost an average of 8.4% of their weight before stopping the medication and regained an average of 0.5% of their weight after 1 year.
- Patients treated for type 2 diabetes lost an average of 4.4% of their weight before discontinuation and an additional 1.3% in the following year.
- Among patients treated for obesity, 55% gained weight after discontinuation, while 45% continued to lose weight or maintain their weight.
- In the diabetic group, 44% gained weight, while 56% maintained or continued to lose weight.
Why patients stop and what to do next
Previous research by the same team has identified two main reasons why patients stop taking these drugs: cost or lack of insurance coverage, and side effects. The most common factor was financial barriers.
Patients taking drugs to treat type 2 diabetes were more likely to restart treatment than those taking drugs to treat obesity. This difference is likely related to more consistent insurance coverage of diabetes prescriptions.
Within 1 year of discontinuing initial GLP-1 medication, many patients sought other weight management strategies.
- 27% switched to another drug (including switching to older generation obesity drugs or semaglutide and tirzepatide)
- 20% restarted their original medication
- 14% continue treatment through lifestyle-focused care from professionals such as nutritionists and exercise specialists
- Less than 1% have undergone metabolic and bariatric surgery
Ongoing support is key to long-term weight management
Researchers say these findings highlight the importance of ongoing, individualized care for people managing obesity, even when medications are discontinued.
“Many patients do not give up on their obesity treatment journey, even if they have to stop their first drug,” Dr. Gasoyan said. “Future studies will weigh the effectiveness of alternative treatment options for obesity in patients who discontinue semaglutide or tirzepatide to help patients and their clinicians make informed decisions.”
