Stopping GLP-1 drugs may quickly reduce their heart-protective benefits

Discontinuing popular GLP-1 medications such as Ozempic, Wegovy, Mounjaro and Zepbound may cause their cardiovascular benefits to fade rapidly, according to a large new study.

Researchers from Washington University School of Medicine in St. Louis found that people with type 2 diabetes who stopped taking GLP-1 drugs faced a progressively higher risk of major cardiovascular events. After two years without treatment, their risk of heart attack, stroke or death was 22% higher than that of people who continued taking the medications.

GLP-1 drugs, including semaglutide and tirzepatide, are widely used to treat type 2 diabetes and obesity. In addition to helping with blood sugar control and weight loss, these medications have been shown to provide cardiovascular benefits.

For the new study, researchers analyzed health records from more than 333,000 U.S. veterans with type 2 diabetes and followed them for up to three years. Among them, 132,551 had been prescribed GLP-1 drugs, while 201,136 had been prescribed sulfonylureas, another class of diabetes medications.

The researchers reassessed treatment status every six months. About 26% of GLP-1 users eventually stopped treatment, while another 23% experienced a treatment interruption lasting at least six months before restarting.

The strongest cardiovascular protection was seen among people who remained on GLP-1 therapy throughout the three-year study. Compared with those taking sulfonylureas, continuous GLP-1 users had an 18% lower risk of major cardiovascular events — equivalent to about four fewer events per 100 people over three years.

The benefits became less pronounced when treatment was interrupted. People who stopped taking GLP-1 drugs and later restarted them had an average 12% reduction in cardiovascular risk, compared with an 18% reduction among those who remained on treatment continuously.

Even a six-month treatment gap was associated with a 4% to 8% increase in cardiovascular risk compared with uninterrupted use. The longer the medications were discontinued, the greater the apparent loss of protection. A one-year interruption was associated with a 14% higher risk, while two years without treatment was associated with a 22% higher risk.

The findings suggest that cardiovascular benefits gained during GLP-1 treatment may diminish relatively quickly once therapy is stopped. Restarting treatment appeared to restore some protection, but not all of it.

"There is enormous exuberance about starting GLP-1 drugs, but not nearly enough attention to what happens when people stop," said senior author Ziyad Al-Aly, a clinical epidemiologist at Washington University School of Medicine and chief of the Research and Development Service at the VA Saint Louis Health Care System.

According to Al-Aly, people may discontinue treatment because of cost, side effects or medication shortages. He noted that stopping therapy may involve more than regaining lost weight, as metabolic changes such as increases in inflammation, blood pressure and cholesterol may also return.

The researchers said the findings highlight the importance of treatment continuity for maintaining the cardiovascular effects of GLP-1 medications. They also emphasized the need to address barriers that can lead patients to discontinue therapy.

The study was published in BMJ Medicine. It was funded by the U.S. Department of Veterans Affairs.

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