The cardiovascular protection offered by GLP-1 drugs such as Ozempic, Wegovy, Mounjaro and Zepbound fades within months of stopping the medication, according to a large study of U.S. military veterans with type 2 diabetes.
Researchers at Washington University School of Medicine in St. Louis and the VA St. Louis Health Care System tracked 333,687 veterans with type 2 diabetes for up to three years: 132,551 who were prescribed a GLP-1 drug and 201,136 prescribed a sulfonylurea, an older class of diabetes medication, as a comparison group. Using a target-trial-emulation design that reassessed outcomes every six months, the team found that veterans who stayed on GLP-1 therapy continuously for three years had an 18 percent lower risk of major cardiovascular events — heart attack, stroke or death — than those on sulfonylureas.
Risk climbs quickly after stopping
That protection did not last once patients discontinued treatment. Six months after stopping, cardiovascular risk was already modestly elevated relative to continuous users; by one year off the drug, risk was 14 percent higher, and by two years off, it was 22 percent higher. The study, published in BMJ Medicine, is among the largest to date to quantify how fast the drugs' cardiovascular benefits erode after use ends.
GLP-1 medications have become some of the most widely prescribed drugs in the country for diabetes and obesity, but cost, side effects and supply shortages routinely interrupt treatment. The new findings suggest those interruptions carry a measurable cardiac cost, not just a resurgence of weight.
"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, Washington University School of Medicine, senior author
The study's authors, whose work was funded by the Department of Veterans Affairs, caution that the veteran population skews older and male, and that the observational design cannot prove causation the way a randomized trial would. Still, they argue the pattern is consistent enough to inform how doctors counsel patients who are considering stopping the drugs, and they are calling for prospective studies to test whether tapering strategies or alternative therapies can preserve cardiovascular gains after discontinuation.