GLP-1 medications are nearly ubiquitous, with approximately one in eight American adults currently taking these drugs. However, discontinuing them may come at a significant cost.
This conclusion stems from a new study by the Washington University School of Medicine, published on Wednesday in the journal BMJ Medicine. The research found that even a brief interruption in GLP-1 therapy for patients with type 2 diabetes increases their risk of heart attack, stroke, and death, and the effects may not be fully reversible. By analyzing electronic health records, researchers tracked over 333,000 adults with diabetes for three years, the vast majority of whom were taking Novo Nordisk's diabetes injection, Ozempic.
Key data points from the study include: * Patients who consistently took GLP-1 drugs for three years experienced an 18% reduction in cardiovascular risk. * Discontinuing GLP-1 medication for just six months negated most of this protective effect, increasing risk by 4% compared to those who continued treatment. * A two-year interruption in therapy pushed this risk up to 22% higher than for those who remained on the medication.
Dr. Ziyad Al-Aly, an epidemiologist at the Washington University School of Medicine and study author, stated in an interview that GLP-1 drugs "do much more than just weight loss." He explained, "They also reduce various back problems, lower cholesterol, reduce blood pressure, decrease insulin resistance, reduce inflammation, and truly provide cardiovascular protection."
He added, "When people stop taking GLP-1 drugs, this cardiovascular protection is lost. More importantly, there is an asymmetry here. It takes years to build cardiovascular protection, but it can be dismantled in half the time." Dr. Al-Aly described this as a "metabolic whiplash," where all the improvements "start moving in the wrong direction" once treatment ends.
These findings are not entirely unexpected. GLP-1 drugs are well-known for their cardiovascular benefits. In 2024, the U.S. Food and Drug Administration approved semaglutide—the active ingredient in Novo Nordisk's Wegovy and Ozempic—for significantly reducing the risk of major cardiovascular events in adults with established heart disease and obesity.
However, this new study provides some of the first large-scale evidence of what happens to patients' hearts, particularly those with diabetes, when they stop taking these medications. The research also highlights an ongoing problem—high discontinuation rates due to access issues and side effects like nausea and vomiting—that healthcare systems have not fully addressed. Multiple studies show discontinuation rates for GLP-1 drugs can range from 36% to 81%.
Dr. Al-Aly emphasized that healthcare providers and patients considering GLP-1 drugs should understand that treatment requires a "long-term" commitment, not just for a few months or even years. He also pointed out the need to address key factors leading to discontinuation, such as proactively managing side effects. In the United States, access issues may improve, especially as major players like Eli Lilly push for employers to expand coverage for weight-loss drugs, and Medicare prepares to cover obesity treatment for the first time.
Ensuring patients stay on therapy "should not be an afterthought," he said. "People need to be aware of the cost of stopping." Pharmaceutical companies are also working to address discontinuation, hoping to develop next-generation weight-loss and diabetes treatments that offer comparable efficacy with fewer unwanted side effects.