Stopping Ozempic? New study reveals surprising weight regain results after GLP-1s

With millions of people using injectable GLP-1 medications like Ozempic, Wegovy or Zepbound, many may wonder what happens if they stop.

Previous clinical trials suggested a discouraging “rebound” effect, where patients regained a significant portion of their lost weight almost immediately after ending treatment.

However, a new study from Cleveland Clinic, published in the journal Diabetes, Obesity and Metabolism, offers a more hopeful perspective on what happens when the injections stop.

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The study looked at nearly 8,000 adults in Ohio and Florida who used semaglutide or tirzepatide for three to 12 months before stopping, according to a press release.

Unlike tightly controlled clinical trials, the researchers looked at “real-world” outcomes where patients often switch from one medication to another.

Overall, patients did not experience significant weight regain in the year after stopping a GLP-1. Among those treated specifically for obesity, the average weight loss before stopping was 8.4%; one year later, they had regained just 0.5% on average.

“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,” said lead study author Dr. Hamlet Gasoyan in the press release.

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This suggests that the rebound seen in clinical trials may be a result of patients being left without alternative support, a scenario that doesn’t have to happen in clinical practice, researchers say.

An estimated 27% of patients transitioned to different medications, including older-generation obesity drugs, while another 20% eventually restarted their original medication once insurance issues or side effects were resolved.

Another 14% transitioned to intensive lifestyle modification programs, working closely with dietitians and exercise specialists.

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Patients who maintained their weight tended to remain engaged with the healthcare system, whether through alternative prescriptions or structured lifestyle support, the researchers noted.

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There were some limitations to the study.

“We included adult patients from a single large integrated health system in Ohio and Florida,” the authors noted. “Patient characteristics and healthcare delivery patterns vary across the U.S., which may limit the generalizability of our findings.”

Some of the observed weight reduction may be associated with other interventions that the researchers were unable to capture.

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“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,” Gasoyan added.