About one in eight U.S. adults takes a glucagon-like peptide-1 receptor agonist (GLP-1 RA) such as semaglutide (sold as Ozempic or Wegovy) or tirzepatide (Zepbound or Mounjaro) for weight loss or to treat type 2 diabetes. Another upside of GLP-1 drugs is that they also reduce the risk of heart attack and stroke or other cardiovascular events by lowering cholesterol and triglyceride levels, blood pressure and inflammation.

When patients stop taking GLP-1 drugs, however, they not only regained weight, but, researchers recently found, their cardiovascular risk increased, too.

People who took GLP-1s for two or two-and-a half years lowered their cardiovascular risk by seven percent and 15 percent, respectively. Unfortunately, the heart benefits were quickly lost when treatment stopped.

The findings highlight the importance of consistency when it comes to GLP-1 treatment. “People who are thinking of starting a GLP-1 RA need to know they will probably be taking this medication for the long haul,” Ziyad Al-Aly, senior author on the study, told TheDoctor.

The researchers looked at data from more than 330,000 U.S. veterans with type 2 diabetes. About 130,000 participants were treated with GLP-1 RAs and about 200,000 were treated with sulfonylureas such as Glucotrol, Amaryl and Diabeta. All were followed for up to three years.

The treatment status of GLP-1 RA users was evaluated every six months. The effect of GLP-1 treatment on cardiovascular risk depended on how long study participants took the medication. Participants who used the drugs during the entire follow-up period had the greatest reduction in cardiovascular risk, 18 percent, compared to those taking sulfonylureas.

About 23 percent of participants on GLP-1 RAs stopped taking the medication for at least six months during the three-year follow-up period and then resumed treatment. People in the study who used GLP-1s for two or two-and-a half years lowered their cardiovascular risk by seven percent and 15 percent, respectively. Participants who took GLP-1 for 18 months or less saw no significant reduction in cardiovascular risk compared to those taking sulfonylureas.

People often stop GLP-1 treatment because they find the side effects intolerable, but discontinuing the drugs was associated with an increase in cardiovascular risk.

Another 26 percent of those on GLP-1 drugs stopped taking the medication and did not restart treatment.

Unfortunately, the heart benefits people gained during the course of GLP treatment were lost when they went off the drugs. Discontinuing GLP-1 RAs for one or two years was associated with a 14 percent or 22 percent increase in cardiovascular risk, respectively, compared to staying on the medication.

People often stop GLP-1 RA treatment because they find the side effects intolerable. Those who experience severe side effects should try to work with their provider to manage them before they decide to discontinue treatment, said Al-Aly, a clinical epidemiologist at Washington University of St. Louis.

The study and a related editorial are published in BMJ Medicine.