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In analysis of more than 20,000 patients, bariatric surgery produced greatest weight loss at 2 years, followed by switching between GLP-1 medications and switching to a non-GLP1 medication
New Cleveland Clinic research published in eClinicalMedicine found that patients who initially took injectable GLP-1 drugs, such as semaglutide (Ozempic/Wegovy) or tirzepatide (Mounjaro/Zepbouund), achieved the greatest weight loss over two years if they later had bariatric surgery. Patients who switched between semaglutide and tirzepatide, stayed on their original medication or moved to another obesity treatment also experienced significant weight loss over the two-year follow-up. Those who discontinued the medication with no further treatment had the smallest weight loss and the least improvement in blood sugar control and blood pressure.
Lead author Hamlet Gasoyan, Ph.D., a researcher with Cleveland Clinic’s Center for Value-Based Care Research, will present the findings on Sunday, Nov. 15, at ObesityWeek 2026, the Obesity Society’s annual meeting in National Harbor, Md.
The percentage of U.S. adults using GLP-1 medications for weight loss climbed to 11% in 2026 from 3% in 2024, according to the 2026 Gallup National Health and Well-Being Index. Overall, 15% said they had used the drugs. Cost, insurance limitations, and side effects remain common reasons patients stop treatment.
“The encouraging news is that, for patients who need to stop their injectable GLP-1 medication, it does not mean that their obesity treatment journey has to end,” said Dr. Gasoyan. “Our findings could support patient-clinician discussions about alternative therapy options for patients who consider switching or stopping injectable semaglutide or tirzepatide.”
The study analyzed electronic health records from 20,486 Cleveland Clinic patients who used semaglutide or tirzepatide for at least three months between 2021 and 2023. Dr. Gasoyan and colleagues compared outcomes across five treatment strategies: remaining on the initial GLP-1 medication, switching between semaglutide and tirzepatide, transitioning to another obesity medication, undergoing bariatric surgery, or discontinuing obesity treatment without additional pharmacological or surgical treatment.
Among the five strategies, bariatric surgery produced the largest average weight loss, with patients losing an average of 28% of their body weight at two years.
“When a patient stops a GLP-1 medication, the most important question is what comes next,” said co-author Ali Aminian, M.D., director of Cleveland Clinic's Bariatric and Metabolic Institute. “In our study, patients who stopped all treatment had the least weight loss and the smallest metabolic benefits, while those who moved on to another effective therapy, particularly bariatric surgery, did considerably better.”
Switching between semaglutide and tirzepatide was associated with greater weight loss, with patients experiencing an average of 16% of weight loss at two years, compared with nearly 11% among those who stayed on the medication they were initially prescribed. Patients who switched from semaglutide to tirzepatide lost more weight than those who stayed on semaglutide. However, among patients who started on tirzepatide, remaining on the original medication was associated with greater weight loss than switching to semaglutide.
Researchers found that transitioning to another obesity medication was associated with an average 8% reduction in body weight at two years. Medications used in that group included liraglutide (Saxenda), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), orlistat (Xenical, Alli), phentermine (Adipex-P, Lomaira), topiramate (Topamax), bupropion (Wellbutrin), pramlintide (Symlin), zonisamide (Zonegran) and dulaglutide (Trulicity).
The benefits weren’t limited to weight loss. Among patients with Type 2 diabetes, bariatric surgery led to the greatest improvements in A1C levels at one year, followed by switching between semaglutide and tirzepatide, remaining on the original medication, and switching to another obesity medication. Patients with hypertension also saw greater reductions in blood pressure when they continued treatment than when they stopped.
By comparison, those who stopped treatment without further weight-management care had the smallest average weight loss, 4%, and experienced minimal improvements in blood sugar control and blood pressure.
“Obesity is a complex, chronic disease, and we cannot approach treatment with a one-size-fits-all approach,” Dr. Gasoyan said. “We will continue our research in this field to help patients choose treatments based on their individualized expected benefits and risks, aligned with their preferences.”
Patients should consult their healthcare provider before discontinuing semaglutide or tirzepatide to discuss alternative treatment options and long-term weight-management strategies.
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation, Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. Cleveland Clinic is consistently recognized in the U.S. and throughout the world for its expertise and care. Among Cleveland Clinic’s 83,000 employees worldwide are more than 6,600 salaried physicians and researchers, and 21,900 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,725-bed health system that includes a 173-acre main campus near downtown Cleveland, 23 hospitals, 300 outpatient facilities, including locations in northeast Ohio; Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2025, there were 15.9 million outpatient encounters, 343,000 hospital admissions and observations, and 336,000 surgeries and procedures throughout Cleveland Clinic’s health system. Visit us at clevelandclinic.org. Follow us at x.com/CleClinicNews. News and resources are available at newsroom.clevelandclinic.org.
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