Sebastian M. Meyhöfer, Bertrand Cariou, Cíntia Cercato, Helen M. Colhoun, John Deanfield, Michelle T. Long, Ole Kleist Jeppesen, A. Michael Lincoff, Ildiko Lingvay, Jorge Plutzky, Philip N. Newsome, Stephen J. Nicholls, Maria Quiroga, Ferruccio Santini, Arun J. Sanyal, Steven E. Kahn, on behalf of the FIDELIO-DKD and FIGARO-DKD Investigators, Donna H. Ryan, Scott S. Emerson, Robert F. Kushner, Kirstine Brown-Frandsen, G. Kees Hovingh, Søren Hardt-Lindberg, Christoffer W. Tornøe
In the SELECT trial, once-weekly subcutaneous semaglutide reduced major adverse cardiovascular events (MACE) by 20% versus placebo in patients with atherosclerotic cardiovascular disease and obesity but without diabetes. We examined semaglutide in SELECT patients at high risk for substantial liver fibrosis in a prespecified secondary analysis. Liver biochemical tests and steatosis risk according to fatty liver index were assessed over 104 weeks. Subgroup analyses of the primary MACE (a composite endpoint including cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) outcome used baseline Fibrosis-4 scores ≥ 1.3, age-specific (≥1.3 (<65 years) or ≥2.0 (≥65 years)) and any age with Fibrosis-4 > 2.67. MACE was reduced by 26% (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63-0.88; P = 0.0004), 21% (HR 0.79; 95% CI 0.63-0.98; P = 0.035) and 34% (HR 0.66; 95% CI 0.39-1.10; P = 0.11), respectively. Semaglutide led to a 28% greater decrease in fatty liver index versus placebo (HR 0.72; 95% CI 0.71-0.73; P < 0.0001). In conclusion, semaglutide reduced MACE versus placebo in patients at risk for substantial liver fibrosis, as seen in the overall SELECT population. ClinicalTrials.gov registration no. NCT03574597.