JAMA Intern Med

Oral semaglutide cuts heart failure events in high-risk diabetes patients

February 4, 2026

In a prespecified secondary analysis of the phase 3b SOUL trial (NCT03914326), once-daily oral semaglutide reduced heart failure (HF) events vs. placebo among patients with T2DM and a history of HF (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.63–0.96). Benefit was driven by patients with HF with preserved ejection fraction (HFpEF; HR, 0.59; 95% CI, 0.39-0.86), not reduced EF (HFrEF; HR, 0.98; 95% CI, 0.70-1.38). Reductions in major adverse CV events were consistent regardless of HF status, and serious adverse events were similar between groups.

Clinical takeaway: In patients with T2DM and established HF—especially HFpEF—oral semaglutide may help reduce HF events without added safety concerns.

Source:

Pop-Busui R, et al; SOUL Study Group. (2026, February 2). JAMA Intern Med. Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41627802/