The benefits of GLP-1 drugs may fade faster than expected when treatment is interrupted.
GLP-1 drugs have quickly moved from niche diabetes treatments to some of the most talked-about medications in the country. Drugs such as semaglutide and tirzepatide are now used by about one in eight U.S. adults, not only for blood sugar control and weight loss, but also for their cardiovascular benefits. But a new study suggests there is an overlooked downside when treatment stops: the health gains may fade faster than many patients realize.
Researchers at Washington University School of Medicine in St. Louis tracked more than 333,000 U.S. veterans with type 2 diabetes over three years. They found that even a six-month break from GLP-1 therapy was linked to a meaningful rise in major cardiovascular events.
Longer gaps were associated with greater risk — reaching as high as a 22% increase in heart attack, stroke, and death after two years without treatment. This increase largely offset the cardiovascular benefits gained while on the drugs.
A Hidden Cost of Stopping Treatment
Published March 18 in BMJ Medicine, the findings show that stopping GLP-1 medications has effects that extend beyond weight gain. The results highlight an increase in cardiovascular risk and reinforce the need for ongoing treatment to maintain heart protection.
“There is enormous exuberance about starting GLP-1 drugs, but not nearly enough attention to what happens when people stop,” said senior author Ziyad Al-Aly, MD, a WashU Medicine clinical epidemiologist and chief of the Research and Development Service at the VA Saint Louis Health Care System. “Many quit after a few months because of cost, side effects or shortages. When they stop, it’s not just weight that comes back; they experience a resurgence in inflammation, blood pressure, and cholesterol. Weight regain is visible; the metabolic reversal is not.”
“Our data suggest this metabolic whiplash is detrimental to heart health,” Al-Aly added. “Restarting the medication helped restore some protection, but only partially, showing that discontinuation leaves a lasting scar.”
GLP-1 benefits build slowly, erode quickly
GLP-1 drugs include semaglutide brands Ozempic and Wegovy, along with tirzepatide brands Mounjaro and Zepbound. After observing that many patients stop these medications soon after starting, Al-Aly investigated how discontinuation affects cardiovascular outcomes, including heart attack, stroke, and death.
The study included 333,687 veterans. Among them, 132,551 were treated with GLP-1 drugs, while 201,136 received sulfonylureas such as glipizide (Glucotrol), glimepiride (Amaryl), and glyburide (Diabeta and others). Researchers followed participants for up to three years.
Treatment status was assessed every six months. During the study, 26% of GLP-1 users stopped taking the medication, and about 23% paused treatment for at least six months before restarting.
Continuous Use Provides the Greatest Protection
Consistent use of GLP-1 medications was strongly linked to fewer cardiovascular events. Compared to patients taking sulfonylureas, those who remained on GLP-1 therapy for the full three years saw the largest benefit — an 18% reduction in risk, equal to about four fewer major cardiovascular events per 100 people.
Patients who used GLP-1 drugs for two or two-and-a-half years before stopping also experienced meaningful reductions in risk (7% and 15%). In contrast, those who took the drugs for less than 18 months before discontinuing showed no significant advantage over the comparison group.
Interruptions reduced the overall benefit. Patients who paused treatment and later resumed it had smaller risk reductions, especially when the gap in therapy was longer. While continuous use led to an 18% reduction, those who interrupted and restarted averaged a 12% reduction. Even a six-month interruption increased risk by 4% to 8% compared to uninterrupted use.
Lasting Effects of Discontinuation
Longer periods without treatment had more serious consequences. Patients who stopped GLP-1 therapy for one or two years without restarting faced a 14% or 22% higher risk of cardiovascular events, respectively, compared to those who continued treatment. In effect, the benefits gained during therapy can fade quickly once the medication is stopped.
These results emphasize the importance of maintaining continuous treatment and suggest that reducing interruptions could help preserve the heart-protective effects of GLP-1 drugs.
“Clinicians should treat adherence to GLP-1 treatment as an important outcome in its own right — not an afterthought,” Al-Aly said. “Health systems need plans in place to help people continue their medication indefinitely, recognizing that GLP-1s treat chronic conditions. That includes proactive management of side effects, candid conversations about the long-term nature of treatment, infrastructure to identify and support patients at risk of stopping and addressing the cost barriers that make GLP-1 therapy unsustainable for many.”
Al-Aly noted that the cardiovascular benefits of GLP-1 medications develop gradually but can decline quickly. Even one year without treatment was enough for participants to lose gains built over years of consistent use. Once those benefits were lost, restarting therapy did not fully restore them.
Reference: “Glucagon-like peptide 1 receptor agonist discontinuation and risks of major adverse cardiovascular events in adults with type 2 diabetes: target trial emulation” by Yan Xie, Taeyoung Choi and Ziyad Al-Aly, 18 March 2026, BMJ Medicine.
DOI: 10.1136/bmjmed-2025-002150
This research was funded by the United States Department of Veterans Affairs. The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication. The contents do not represent the views of the US Department of Veterans Affairs or the US Government.
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