Oral semaglutide vastly reduces heart attacks, strokes in people with type 2 diabetes, suggests study

Both the injectable and oral forms of semaglutide, a glucagon-like peptide-1 receptor agonist, have gained recent attention for their effectiveness against weight gain, high blood sugar, and even alcohol cravings.

A new clinical trial, co-led by endocrinologist and diabetes expert John Buse, MD, PhD, and interventional cardiologist Matthew Cavender, MD, MPH, at the UNC School of Medicine has shown that the oral form of semaglutide can significantly reduce cardiovascular events in people with type 2 diabetes, atherosclerotic cardiovascular disease, and/or chronic kidney disease.

“Heart attacks and strokes are among the most common and devastating complications of diabetes,” said Buse, who is the Verne S. Caviness Distinguished Professor of Medicine and Director of the UNC Diabetes Care Center. “Semaglutide has been a main stay of our efforts to reduce heart attack and stroke in people with diabetes. Having an oral option to deliver this highly effective therapy is a big advance.”

[caption id="attachment_37583" align="alignright" width="231"] John B. Buse, MD, PhD[/caption]

Results from the rather large, international trial were published in the New England Journal of Medicine and presented at the American College of Cardiology's Annual Scientific Session & Expo in Chicago, Illinois.

Type 2 diabetes is a progressive disease that affects one’s ability to control blood sugar levels.

People with the condition need to closely monitor their diet and activity and may need to take medications as their blood sugar becomes more difficult to manage. Those with type 2 diabetes are at a significantly higher risk of cardiovascular disease because they may develop high blood pressure, high cholesterol, or both, as a result of uncontrolled blood sugar.

Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, have shown much potential for lowering blood sugar, but little is known about whether the oral form of semaglutide actually decreases major cardiovascular events, such as heart attacks and stroke.

The Semaglutide cardiOvascular oUtcomes triaL (SOUL) recruited 9,650 people for the study who have pre-existing cardiovascular disease, such as coronary artery disease, symptomatic peripheral arterial disease, cerebrovascular disease, or chronic kidney disease. The trial was sponsored and funded by pharmaceutical company Novo Nordisk, Inc.

Participants were divided into a placebo group (no medication) and a drug group to see if those taking oral semaglutide were more or less likely to experience major cardiac events. Both groups were given standard-of-care glucose-lowering and cardiovascular risk-reducing therapies according to local guidelines. Those in the medication group took a once-daily 14mg dose of oral semaglutide.

Researchers found that oral semaglutide decreased the risk of major cardiovascular events by 14% compared to placebo across age and gender. Of all types of major cardiac events studied in the clinical trial, nonfatal myocardial infarction saw the greatest reductions in risk.

The effect of oral semaglutide on cardiovascular outcomes was consistent with other clinical trials involving injectable semaglutide, but more trials are needed to determine if one method may be more effective than the other at reducing major cardiovascular events.

References: Authors: Darren K. McGuire, M.D., M.H.Sc., Nikolaus Marx, M.D., Sharon L. Mulvagh, M.D., John E. Deanfield, M.D., Silvio E. Inzucchi, M.D., Rodica Pop-Busui, M.D., Ph.D., Johannes F.E. Mann, M.D., +11 , for the SOUL Study Group*Author Info & Affiliations Published March 29, 2025 DOI: 10.1056/NEJMoa2501006