Patients with type 2 diabetes who stop taking GLP-1 receptor agonist drugs such as semaglutide lose much of the medication's heart-protective benefit within months, according to a study published in BMJ Medicine.
Researchers at Washington University School of Medicine in St. Louis analyzed U.S. Department of Veterans Affairs health records from 2017 through 2023, comparing cardiovascular outcomes for 132,551 veterans with type 2 diabetes prescribed a GLP-1 drug against 201,136 prescribed a sulfonylurea, an older class of diabetes medication. Patients who stayed on a GLP-1 drug continuously for three years had an 18% lower risk of major cardiovascular events — heart attack, stroke or death — compared with the sulfonylurea group. That protection faded quickly once treatment stopped: a six-month gap in GLP-1 use was linked to a 4% higher risk of those events relative to continuous use, a one-year gap to a 14% higher risk, and a two-year gap to a 22% higher risk.
An Observational Study, Not a Trial
The study used a design called target trial emulation, applying the statistical framework of a randomized trial to retrospective health-record data rather than randomly assigning patients to stop or continue their medication. The authors, who received funding from the Department of Veterans Affairs, acknowledged in the published paper that the study population skewed older and mostly male because it drew on the veteran health system, that it was limited to people with type 2 diabetes rather than the broader population now using GLP-1 drugs for weight loss, and that despite adjusting for numerous factors, "residual confounding" could not be entirely ruled out. The protocol also was not pre-registered.
"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."
Dr. Ziyad Al-Aly, senior author, Washington University School of Medicine
GLP-1 drugs, originally developed for diabetes, have become widely used for weight loss under brand names including Ozempic, Wegovy and Zepbound, and cost and insurance coverage gaps are a common reason patients cycle on and off the medications. The new findings add cardiovascular risk to the list of consequences tied to that pattern, alongside the weight regain and blood-sugar rebound documented in earlier research on the same population.
The authors say restarting the drugs after a gap partially restores the cardiovascular benefit but does not fully erase the risk accumulated while off treatment — a finding they argue should inform conversations between patients and doctors about the trade-offs of interrupting therapy for cost or supply reasons rather than stopping it outright.
