Semaglutide on liver fibrosis and heart outcomes in patients at high risk of liver fibrosis: a prespecified analysis of the SELECT randomized trial.

Summary

In a prespecified subgroup of SELECT, semaglutide reduced MACE by 26% in patients with FIB-4 ≥1.3 and by 21% using age-specific FIB-4 thresholds; an even larger but non-significant 34% reduction was observed at FIB-4 >2.67. Semaglutide also produced a 28% greater decrease in fatty liver index over 104 weeks compared with placebo.

Key Findings

• Semaglutide reduced MACE by 26% for FIB-4 ≥1.3 (HR 0.74, 95% CI 0.63-0.88) and by 21% using age-specific FIB-4 thresholds (HR 0.79, 95% CI 0.63-0.98).
• A non-significant 34% MACE reduction was observed for FIB-4 >2.67 (HR 0.66, 95% CI 0.39-1.10).
• Semaglutide achieved a 28% greater reduction in fatty liver index versus placebo over 104 weeks (P<0.0001).

Clinical Implications

Semaglutide may be prioritized for ASCVD patients with obesity who also have elevated FIB-4, given concurrent MACE reduction and improvements in steatosis indices; integrating FIB-4 could help risk stratify for cardiometabolic therapy.

Limitations

• Secondary analysis; subgroup sizes and event counts by FIB-4 strata are not detailed in the abstract.
• FIB-4 and fatty liver index are indirect biomarkers and do not replace histology or elastography.

Future Directions

Prospective studies using imaging or histologic fibrosis endpoints can validate whether fibrosis risk enrichment modifies semaglutide’s cardiovascular benefit; explore integration with NAFLD/NASH care pathways.