Stopping treatment with GLP-1 medications, such as semaglutide and tirzepatide, is associated with an increased risk of major cardiovascular events, according to a study published on March 18. The research was conducted by Washington University School of Medicine in St. Louis and followed more than 333,000 U.S. veterans with type 2 diabetes over three years.
The findings are significant because GLP-1 drugs have become increasingly popular for both diabetes management and weight loss, with about one in eight U.S. adults now taking these medications. While the drugs are known to provide cardiovascular benefits, the study found that discontinuing them can lead not only to weight regain but also to a higher risk of heart attack, stroke, and death compared to continued use.
Researchers observed that stopping or interrupting GLP-1 treatment for as little as six months led to a notable increase in the risk of major cardiovascular events. The longer patients were off the medication, the greater their risk—up to a 22% increase after two years without GLP-1s—effectively erasing much of the benefit gained during treatment.
"There is enormous exuberance about starting GLP-1 drugs, but not nearly enough attention to what happens when people stop," said Ziyad Al-Aly, MD, senior author of the study 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." Al-Aly added: "Our data suggest this metabolic whiplash is detrimental to heart health. Restarting the medication helped restore some protection, but only partially, showing that discontinuation leaves a lasting scar."
The study compared participants prescribed GLP-1s with those prescribed sulfonylureas for type 2 diabetes management. Continuous use of GLP-1s over three years resulted in an 18% reduction in major cardiovascular events compared to sulfonylureas. However, interruptions or discontinuations reduced or eliminated these benefits.
Al-Aly emphasized that maintaining adherence should be considered an important outcome: "Clinicians should treat adherence to GLP-1 treatment as an important outcome in its own right - not an afterthought." He also called for health systems to develop strategies supporting long-term use by addressing side effects and cost barriers.
The researchers concluded that continuous treatment is crucial for sustained heart protection from GLP-1 medications and suggested that strategies be developed to reduce interruptions in therapy.
