Semaglutide 2.4 mg weekly reduced major cardiovascular events by 28% and composite heart failure outcomes by 21% in patients with obesity and existing heart failure, regardless of heart failure subtype.
HR 0.72 for MACESemaglutide reduced major adverse cardiovascular events by 28% in patients with obesity and existing heart failure
What the researchers found
Among 4,286 patients with heart failure at enrollment (out of 17,604 total), semaglutide 2.4 mg weekly significantly improved all cardiovascular outcomes compared to placebo: MACE HR 0.72 (95% CI 0.60–0.87), composite heart failure endpoint HR 0.79 (0.64–0.98), cardiovascular death HR 0.76 (0.59–0.97), and all-cause death HR 0.81 (0.66–1.00).
Benefits were consistent across heart failure subtypes: HFrEF showed MACE HR 0.65 (0.49–0.87) and HFpEF showed MACE HR 0.69 (0.51–0.91). No significant treatment interaction was observed across age, sex, BMI, NYHA status, or diuretic use subgroups. Serious adverse events were less frequent with semaglutide regardless of heart failure subtype.
Why it matters
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.
How the study worked
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.
What this study cannot tell us
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.
How to read the evidence
This is a prespecified subanalysis of a large-scale, randomized, double-blind, placebo-controlled phase 3 trial (SELECT) published in The Lancet. While subgroup analyses are inherently less definitive than primary endpoints, the large sample size, rigorous methodology, and consistency of findings across subgroups make this very strong evidence.
When this study was published
Published in 2024 in The Lancet with data from 2018–2021, this is among the most current high-quality evidence for semaglutide's cardiovascular effects in heart failure patients.
The bigger picture
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.
Questions still open
- Should semaglutide become a standard therapy for obese patients with heart failure regardless of ejection fraction?
- How do the cardiovascular benefits of semaglutide compare to established heart failure therapies like SGLT2 inhibitors in this population?
- Would even higher doses or longer treatment duration produce greater cardiovascular benefits in heart failure patients?
Common questions
Does semaglutide help with heart failure or just weight loss?
Does semaglutide work for all types of heart failure?
Read the original research
Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial.
Lancet (London, England), 404(10454), 773-786
Citation
Deanfield, John; Verma, Subodh; Scirica, Benjamin M; Kahn, Steven E; Emerson, Scott S; Ryan, Donna; Lingvay, Ildiko; Colhoun, Helen M; Plutzky, Jorge; Kosiborod, Mikhail N; Hovingh, G Kees; Hardt-Lindberg, Søren; Frenkel, Ofir; Weeke, Peter E; Rasmussen, Søren; Goudev, Assen; Lang, Chim C; Urina-Triana, Miguel; Pietilä, Mikko; Lincoff, A Michael. (2024). Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial.. Lancet (London, England), 404(10454), 773-786. https://doi.org/10.1016/S0140-6736(24)01498-3