Tejal Somvanshi
If you take a GLP-1 drug such as Ozempic, Wegovy, Mounjaro or Zepbound, the decision to stop can feel like the end of the road. Cost, insurance limits and side effects push many people off these medications. A new Cleveland Clinic study of 20,486 patients says what comes after stopping GLP-1 drugs matters far more than the stop itself.
The study, published in the journal eClinicalMedicine, drew on electronic health records from 20,486 Cleveland Clinic patients. All had used semaglutide or tirzepatide for at least three months between 2021 and 2023. Lead author Hamlet Gasoyan, Ph.D., presented the findings on Sunday, Nov. 15, at ObesityWeek 2026 in National Harbor, Md. Researchers compared five paths after that initial use. The groups were followed for two years. Surgery produced the largest average loss, 28% of body weight. Switching between the two drugs produced 16%. Staying on the original drug produced nearly 11%. Moving to another obesity medication produced 8%. Stopping all treatment produced 4%.
Quitting all obesity care left patients with a 4% average weight loss at two years. It also erased most of the progress on blood sugar and blood pressure. Patients who stayed on some form of treatment kept far more of their loss. For anyone facing an insurance denial or a copay they cannot sustain, the lesson is simple. Do not stop without a next step already in place.
The Two Drugs Behind the Numbers
Semaglutide is sold under the brand names Ozempic and Wegovy. Tirzepatide is sold as Mounjaro and Zepbound. Both are injectable GLP-1 medicines. Patients in the study had used one of these two drugs for at least three months. The researchers then looked at what those patients did next. They measured the weight each patient lost over the following two years.
Switching Direction Changed the Result
Not all switching worked the same way. Patients who moved from semaglutide to tirzepatide lost more weight than those who stayed on semaglutide. The pattern ran the other way for tirzepatide starters. Among patients who began on tirzepatide, staying on tirzepatide was linked to greater weight loss than switching down to semaglutide. The study reports associations, not proof that one drug caused the difference.
Older Pills Still Beat Quitting Altogether
The third option was a different obesity medication. That group lost an average of 8% of body weight at two years. The medicines used included liraglutide (Saxenda), phentermine-topiramate (Qsymia) and naltrexone-bupropion (Contrave). Others were orlistat (Xenical, Alli), phentermine (Adipex-P, Lomaira), topiramate (Topamax), bupropion (Wellbutrin), pramlintide (Symlin), zonisamide (Zonegran) and dulaglutide (Trulicity). For patients who cannot get a GLP-1 covered, they remain an option worth discussing.
Blood Sugar, Blood Pressure, and a Rapid Rise in Use
The benefits went beyond the scale. Among patients with Type 2 diabetes, bariatric surgery led to the greatest improvement in A1C at one year. A1C is a blood test that tracks average blood sugar over several months. Switching between the two drugs came next, then staying on the original drug, then moving to another obesity medication. Patients with high blood pressure also saw larger falls when they stayed on treatment than when they stopped. Nationally, the share of U.S. adults using a GLP-1 drug for weight loss reached 11% in 2026. That was up from 3% in 2024. The figures come from the 2026 Gallup National Health and Well-Being Index. Overall, 15% said they had used these drugs. Cost, insurance limits and side effects remain the main reasons people stop.
The clearest pattern in the data is the asymmetry. Stepping up from semaglutide to tirzepatide beat staying on semaglutide. Stepping down from tirzepatide to semaglutide trailed staying on tirzepatide. An older pill, at 8%, still delivered roughly twice the two-year loss of quitting with no further care, 4%.
Frequently Asked Questions
What is the best way to keep weight off after stopping GLP-1 drugs?
Bariatric surgery produced the greatest two-year weight loss, 28% of body weight. Switching between semaglutide and tirzepatide came next at 16%. Staying on the original drug produced nearly 11%, another obesity medication 8%, and stopping all treatment 4%.
Should you switch from semaglutide to tirzepatide?
Patients who moved from semaglutide to tirzepatide lost more weight than those who stayed on semaglutide. The reverse was not true. Tirzepatide starters lost more by staying on tirzepatide than by switching to semaglutide. A clinician can help weigh the change against cost and side effects.
Which non-GLP-1 obesity medications were studied, and how well did they work?
Researchers counted patients who moved to a different obesity medication. That group lost an average of 8% of body weight at two years. The medicines included liraglutide (Saxenda), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), orlistat, phentermine, topiramate, bupropion, pramlintide, zonisamide and dulaglutide (Trulicity).
The study does not tell patients which path to pick. It does give them five concrete options to raise with a prescribing clinician. Anyone thinking about pausing or switching semaglutide or tirzepatide should talk to their provider first, and bring this comparison with them.
