Semaglutide Reduced Heart Attacks, Strokes, and Heart Failure Events in Obese Patients With Heart Failure in the SELECT Trial

Prespecified subanalysis of the SELECT trial, a randomized, double-blind, multicenter, placebo-controlled, event-driven phase 3 trial conducted across 41 countries. 17,604 adults aged 45+ with BMI ≥27 and established cardiovascular disease were randomized 1:1 to semaglutide 2.4 mg weekly or placebo, titrated over 16 weeks. Patients were subclassified by heart failure status and type (HFpEF, HFrEF, or unclassified). Enrollment ran from October 2018 to March 2021.

Heart failure in obese patients is extremely common and difficult to treat, with limited proven therapies especially for HFpEF. This Lancet analysis from one of the largest cardiovascular outcomes trials ever conducted provides strong evidence that semaglutide benefits heart failure patients regardless of subtype — a finding that could change prescribing guidelines and help millions of patients at the intersection of obesity and heart failure.

The SELECT trial has been transformative in establishing semaglutide's cardiovascular benefits beyond glucose and weight control. This heart failure subanalysis is particularly important because it shows benefits in both HFpEF and HFrEF — conditions that historically respond very differently to treatment. Combined with other SELECT subanalyses, this data positions semaglutide as a potential cornerstone therapy for cardiometabolic disease.

This is a prespecified subgroup analysis, which carries less statistical power than the primary trial endpoint. Heart failure classification was investigator-defined rather than adjudicated, and 15.5% of heart failure patients were unclassified. The trial was sponsored by Novo Nordisk. Patients with severe heart failure (NYHA Class IV) may have been underrepresented. The trial excluded patients with diabetes, limiting generalizability to the diabetic heart failure population.