SOUL
A Heart Disease Study of Semaglutide in Patients with Type 2 Diabetes (Semaglutide cardiOvascular oUtcomes triaL)
Patient / Population Intervention / Exposure Comparison Outcome
In 9,650 patients with type 2 diabetes and ASCVD, CKD, or both, oral semaglutide reduced major adverse cardiovascular events compared with placebo (HR 0.86, 95% CI 0.77-0.96).
N
9,650
Design
Double-blind placebo-controlled RCT, event-driven superiority
Endpoint
Composite of CV death, nonfatal MI, or nonfatal stroke (3-point MACE)
Relevance
2
ResultPrimary event 12.0% with oral semaglutide vs 13.8% with placebo (HR 0.86, 95% CI 0.77-0.96; P=0.006) over mean 47.5 months, a 14% relative risk reduction driven largely by fewer MIs.
McGuire DK, Marx N, Mulvagh SL, et al. N Engl J Med. 2025;392(20):2001-2012. 10.1056/NEJMoa2501006
Discussion & critique
MACE benefit modest and driven mainly by the MI component with no reduction in CV or all-cause death, and most patients were not on SGLT2 inhibitors at baseline. First CVOT to show an oral GLP-1 agonist lowers cardiovascular events.