ATLANTA — More than half of the people who stop using GLP-1 drugs regain at least some of the weight within a year, new real-world data showed.
The new findings, from a large national claims database, “corroborate the clinical trial data that treatment discontinuation leads to weight recurrence. Optimizing and personalizing the approach toward treating obesity and maximizing gastrointestinal tolerability will maximize long-term use and long-term benefits of weight reduction,” study author Michael A. Weintraub, MD, an endocrinologist at New York University Langone Health, New York City, told Medscape Medical News.
Weintraub reported the data on November 5, 2025, at Obesity Week 2025. “Treatment discontinuation leads to weight recurrence in clinical trials, but few real-world studies have evaluated this issue,” Weintraub said in his introduction.
Asked to comment, session moderator John W. Apolzan, PhD, associate professor in clinical nutrition and metabolism at the Pennington Biomedical Research Center, Baton Rouge, Louisiana, told Medscape Medical News, “I think this was a continuation of what we’re realizing, that these obesity classes of drugs can’t be discontinued, as it can have negative effects and cause long-term weight regain. It’s like many other prescription medications that people go on, be it hypertensives or anything like that. Once you’re on them, you tend to stay on them and you don’t go off them.”
The retrospective cohort study included US adults from January 2010 to June 2024 who filled GLP-1 prescriptions recorded in Optum’s Market Clarity database, which links electronic health records with claims data. Of 1,230,320 who had filled GLP-1 prescriptions for type 2 diabetes (T2D) or overweight/obesity, 18,228 discontinued after having lost at least 5% body weight and met other study criteria. Of those, 69.5% (n = 12,671) had T2D and 30.5% (n = 5557) did not.
The study population had a mean age of 55 years, were 65% women, and had a mean BMI 39. Most (77%) were White individuals. They were geographically distributed all around the US. Their most common comorbidities were dyslipidemia (73%), gastrointestinal reflux (36%), and obstructive sleep apnea (32%).
Of the total 18,228, 54% had taken semaglutide, 39% liraglutide, and 7% tirzepatide. On average, they had taken the drug for 258 days, or just over 8 months, before discontinuing it. Those with T2D took it longer, 280 days vs 210 days among those without diabetes. Of the entire database cohort of more than 1.2 million, 55% were still using the GLP-1 drug after 6 months, dropping down to 38% by 12 months. And again, persistence was higher among those with T2D at both timepoints (41.8% vs 30.2% at 12 months).
Weight loss at the time of GLP-1 discontinuation was 10.1% overall, 9.7% for those with T2D, and 11.1% for those without. Weight loss was also greater with higher baseline BMI, ranging from 8.2% for those with BMI < 25 to 10.3% among those with baseline BMI ≥ 40.
For the entire group, weight recurrence rose with longer time since discontinuing the GLP-1, from 4.5% total body weight gain at 3 months to 5.9% at 6 months to 6.7% at 9 months, and 7.5% at 1 year. At 6 months, weight regain was 5.6% for those with T2D and 6.7% for those without.
Overall, 42% did not regain weight after discontinuing GLP-1s, and those with T2D were actually more likely to maintain their weight, 44% vs 37% among those without diabetes.
The degree of weight recurrence after discontinuing GLP-1s was greater in those who had lost the most weight with the drugs, ranging from 5.1% among those who had lost < 10% initially to 9.2% for those who had lost ≥ 20%.
“Further areas of analysis would be to determine the differential factors in those who maintained their weight loss and those who experienced weight recurrence following the discontinuation of a GLP-1s, and ultimately, more strategies are necessary to enhance treatment persistence to attain sustained weight loss and optimal patient outcomes,” Weintraub concluded.
During the discussion period, an audience member pointed out that the 42% who were able to maintain their weight after discontinuing GLP-1s was actually higher than previously reported. Weintraub replied, “Yes…The converse is actually true, that we saw a good deal of patients were able to maintain this degree of weight loss…Was it structured lifestyle changes that were implemented? Was it switching to another formulation of a GLP-1 drug that we couldn’t capture in the claims data? That’s still something we need to differentiate.”
Weintraub and Apolzan had no disclosures.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.