What happens after patients stop GLP-1 drugs? A real-world Cleveland Clinic study
An analysis of nearly 8,000 patients found that most avoided major weight regain after a year, often by restarting the drug or moving to another treatment.
The use of injectable GLP-1 drugs keeps rising, and one open question is what happens to people’s weight once they come off them. A new analysis from Cleveland Clinic offers some of the largest real-world data on this so far, and the picture differs from what earlier clinical trials suggested.
What the study looked at
Researchers reviewed the records of nearly 8,000 adults in Ohio and Florida who had begun an injectable GLP-1 medication, either semaglutide (sold as Ozempic and Wegovy) or tirzepatide (sold as Mounjaro and Zepbound), for obesity or type 2 diabetes, and then came off it within three to twelve months. The team tracked what those patients did next and how their weight changed over the following year. The work was published in the journal Diabetes, Obesity and Metabolism and led by Hamlet Gasoyan of the clinic’s Center for Value-Based Care Research.
What they found
On average, coming off the medication did not lead to the large weight regain seen in earlier randomized trials, where patients had regained more than half of their lost weight within a year. The real-world numbers were steadier. People treated for obesity had lost about 8.4% of their body weight beforehand, and a year later had regained only around 0.5% on average. People treated for type 2 diabetes had lost about 4.4% beforehand, and lost a further 1.3% over the next year.
Individual results varied widely. In the obesity group, 55% gained weight in the year afterward while 45% kept losing or held steady. In the diabetes group, 44% gained weight and 56% kept losing or held steady.
Why the real-world picture differs
The researchers attribute the gap to what patients did next. Many did not end treatment altogether. Within a year of coming off their first injectable, about 20% had restarted their original medication and about 27% had moved to a different one, such as an older obesity drug or a switch between semaglutide and tirzepatide. About 14% kept working on their weight through lifestyle visits with professionals like dietitians or exercise specialists. Fewer than 1% went on to metabolic or bariatric surgery. The group’s earlier work found that cost and insurance limits were the leading reason people came off the drugs, ahead of side effects, and that those treated for diabetes were more likely than those treated for obesity to resume, which the researchers tie to steadier insurance coverage for diabetes prescriptions.
Where it stands
The authors say the results point to the value of ongoing, personalized support for people being treated for obesity, even after a given medication ends, and they plan to study how well the various follow-up options work. Semaglutide and tirzepatide are prescription-only medicines, and questions of eligibility, dosing, side effects, and what comes after a medication ends are matters for the product label and a prescriber.
General information, not medical advice. Care decisions are between you and a licensed prescriber.