Researchers at Washington University School of Medicine in St. Louis tracked more than 333,000 U.S. veterans with type 2 diabetes for three years and found that interrupting or stopping GLP-1 treatment for as little as six months was associated with a meaningful increase in major cardiovascular events. The longer patients stayed off treatment, the larger the increase.

The drugs in question are semaglutide (sold as Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound), now used by about one in eight U.S. adults according to the report. They are prescribed for type 2 diabetes and weight loss, and they are also known to provide cardiovascular benefits, which is the part of the picture this study follows after the prescriptions stop.

Key results

Of the 333,687 veterans analyzed, 132,551 had been prescribed GLP-1 drugs and 201,136 sulfonylureas such as glipizide, glimepiride and glyburide. Compared with the sulfonylurea group, people who stayed on GLP-1 therapy for the full three years had an 18% lower risk of major cardiovascular events, which the researchers translated to about four fewer events per 100 people over three years.

That protection did not survive interruption well. People who stopped for one year without restarting had a 14% higher risk than continuous users, rising to 22% after two years off, and even a six-month gap was associated with a 4% to 8% increase.

Why adherence is the story

This is not a small-print finding, because leaving is the norm rather than the exception: 26% of GLP-1 users in the study quit altogether and roughly 23% had a gap of at least six months before restarting. Senior author Ziyad Al-Aly said many quit because of cost, side effects or shortages, and that when they do, "it's not just weight that comes back."

Restarting helped. Those who stopped and resumed averaged a 12% risk reduction versus 18% for continuous users, which Al-Aly described as discontinuation leaving "a lasting scar."

Limitations

This is an analysis of prescription and outcome records, not a randomized trial, so the results are associations rather than proof of cause. The cohort was U.S. veterans with type 2 diabetes, a population that is not representative of everyone taking these drugs, and the comparison group was people on a different diabetes medication rather than no treatment.

Bottom line

The authors conclude that cardiovascular protection from GLP-1 treatment appears to build gradually and fade fast, and that adherence deserves to be treated as an outcome in its own right. What the data cannot settle is why so many people stop, and whether fixing cost and side-effect barriers would close the gap.