Regaining weight after stopping a GLP-1 medication is a commonly reported side effect — but going off the drug may also result in the loss of other health improvements, as well.
New clinical trial analysis of the SURMOUNT-4 trial found that a majority of people who stopped taking tirzepatide (marketed for weight loss under the brand name Zepbound) not only gained back at least 25 percent of weight lost on the drug — they also experienced a significant reversal of its heart and metabolic benefits.
“These findings further cement the idea that GLP-1 medications are meant to be taken indefinitely, just like any other chronic disease medication for other chronic diseases,” says Spencer Nadolsky, DO, an obesity medicine doctor in Portage, Michigan and founder of the online obesity clinic Vineyard. Dr. Nadolsky was not involved in the study.
What the Study Found
The team analyzed health data from about 300 participants who had obesity and at least one weight-related complication (most were female and were 47 years old on average). The participants had taken tirzepatide for 36 weeks and experienced both weight loss and cardiometabolic improvements like decreases in waist size, blood pressure, and LDL “bad” cholesterol. The study was funded by the maker of Zepbound, Eli Lilly.
Researchers found that most participants (82 percent) experienced at least a 25 percent weight regain a year after going off the GLP-1.
In addition, those who regained more weight post-Zepbound had a more significant reversal of heart and metabolism benefits they achieved while on the drug — including waist size, blood pressure, LDL cholesterol, and blood sugar levels — than those who maintained their weight loss.
What Typically Happens When You Stop a GLP-1 Medication?
Previous research has shown that it’s almost certain you’ll regain some amount of weight if you stop taking a GLP-1 medication. An earlier study using the SURMOUNT-4 data showed just that — participants regained weight within a year of quitting Zepbound.
This new analysis took the data further by categorizing the different levels of weight loss or regain with cardiometabolic health outcomes.
“The participants that regained the most amount of weight have the most significant reversal of cardiometabolic benefits," says Dr. Nadolsky. People who kept the weight off were able to mostly maintain the metabolic improvements Zepbound helped them achieve, with the exception of blood pressure, he says.
The study authors recommend future research to dig deeper into better strategies for weight reduction maintenance post-GLP-1, noting that the current study limitations include a lack of detailed lifestyle measures — like whether participants kept up with exercise and positive diet changes — that could add to the depth of the findings.
“It would be nice to see the difference in lifestyle in those various categories of who didn't regain that much weight versus those who regained the most along with the various cardiometabolic markers like blood pressure changes,” adds Nadolsky.
“Obviously, the direct pricing with the manufacturers could help someone at least stay on a very low dose and spread it out further if needed to save money. You can use non-GLP-1 medications that are generic and cheaper, like phentermine and topiramate, as well,” says Nadolsky.
Preventing weight regain after stopping a GLP-1 treatment generally requires careful reinforcement of lifestyle changes that support weight loss, such as a healthy diet, regular exercise, and getting enough sleep.
If you lose access to your GLP-1, talk to your doctor, Nadolsky recommends. “Lifestyle may not be enough, but you can try your best. If needed, you may want to look into non-GLP medicines, along with maybe a low-dose spread out beyond one week at a time.”
EDITORIAL SOURCES
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Resources
Horn DB et al. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. JAMA Internal Medicine. November 24, 2025.
Emily Kay Votruba has copy edited and fact-checked for national magazines, websites, and books since 1997, including Self, GQ, Gourmet, Golf Magazine,Outside, Cornell University Press, Penguin Random House, and Harper's Magazine. Her projects have included cookbooks (Padma Lakshmi's Tangy Tart Hot & Sweet), self-help and advice titles (Mika Brzezinski's Know Your Value: Women, Money, and Getting What You're Worth), memoirs (Larry King's My Remarkable Journey), and science (Now You See It: How the Brain Science of Attention Will Transform How We Live, Work, and Learn, by Cathy Davidson). She started freelancing for Everyday Health in 2016.
Cristina Mutchler is an award-winning journalist with more than a decade of experience covering health and wellness content for national outlets. She previous worked at CNN, Newsy, and the American Academy of Dermatology. A multilingual Latina and published bilingual author, Cristina has a master's degree in Journalism from the E.W. Scripps School of Journalism at Ohio University.
