Oral semaglutide found to lower risk of heart failure events in people with type 2 diabetes

Time to First Composite Heart Failure (HF) Outcome by Treatment and Baseline HF Status and Subtype. Credit: JAMA Internal Medicine (2026). DOI: 10.1001/jamainternmed.2025.7774

An international clinical trial has found that an oral form of semaglutide, a widely used diabetes drug, reduced the risk of serious heart failure events in people with type 2 diabetes who already had heart failure. The findings, published in JAMA Internal Medicine, come from a large randomized trial of nearly 9,650 adults who have both type 2 diabetes and either cardiovascular disease or chronic kidney disease. Researchers followed participants for nearly four years as part of the Semaglutide Cardiovascular Outcomes, or SOUL, Trial. The results are from a secondary analysis of those data.

Rodica Pop-Busui, M.D., Ph.D., professor and chief of the Division of Endocrinology, Diabetes and Clinical Nutrition, the Jordan Schnitzer Chair in Diabetes, and director of the Harold Schnitzer Diabetes Health Center at Oregon Health & Science University, is senior author of the study. She said among those with a history of heart failure, study participants who took oral semaglutide were about 22% less likely than those who received a placebo to experience a combined outcome of heart failure hospitalization, an urgent heart failure visit, or cardiovascular death.

The benefit was especially notable in participants with heart failure with preserved ejection fraction, or HFpEF, a common and difficult-to-treat form of heart failure. In participants without a prior history of heart failure, the drug did not significantly reduce heart failure events.

“Heart failure, especially HFpEF, is the most common form of heart failure in people with type 2 diabetes and obesity,” Pop-Busui said. “These results give doctors more guidance when choosing treatments. Patients with both diabetes and HFpEF often have worse outcomes because they tend to have more underlying health problems that affect the heart.”

Type 2 diabetes and heart failure

Heart failure is a leading cause of hospitalization and death in people with type 2 diabetes. While several diabetes drugs have been shown to reduce heart attacks and strokes, fewer have demonstrated clear benefits for heart failure—particularly in patients who already have the condition.

Semaglutides are GLP-1 receptor agonists, and also are sometimes used as weight-loss drugs.

“Our findings also documented that oral semaglutide was not only effective in reducing further heart failure-related outcomes but was also a safe option in people with diabetes and heart failure, thus refuting prior potential concerns related to safety,” Pop-Busui said. “In addition, the effectiveness of a once-daily oral formulation is important as it provides an easier therapeutic option for those who may be frailer or may not have the capability for taking injections.”

The new findings suggest that oral semaglutide may offer added protection for high-risk patients who are managing both diabetes and heart failure. For clinicians, the results could help guide medication choices when treating individuals with overlapping heart and metabolic disease. For patients, the study adds evidence that some diabetes treatments may not only lower blood sugar, but also reduce the risk of serious heart complications.

Researchers said that the heart failure analysis was secondary, meaning the trial was not originally designed specifically to measure those outcomes. Still, the results add to growing evidence that certain diabetes medications can improve long-term cardiovascular health.

GLP-1RAs shown to reduce risk of cardiovascular death