Antidiabetic and lipid‐lowering medication use inversely linked with serum biomarkers of liver fibrosis

AIMS: The impact of antidiabetic and lipid-lowering medications on fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH) is poorly understood. We evaluated associations between the use of these medications and serum liver fibrosis biomarkers, and whether they vary by genetic factors. MATERIALS AND METHODS: This cross-sectional study used baseline medication and fibrosis biomarker (aspartate aminotransferase-to-platelet ratio index [APRI], Enhanced Liver Fibrosis [ELF], Fibrosis-4 Index (FIB-4) and FibroSure/FibroTest) data from two phase 3 trials (N = 1649) of MASH with bridging fibrosis (NCT03053050, N = 785) or compensated cirrhosis (NCT03053063, N = 864). A weighted polygenic risk score (wPRS) for MASH was derived for participants of European ancestry (N = 742) using six genetic variants. Least-squares means and 95% confidence interval (CIs) were derived using multivariable linear regression. RESULTS: Combined use of antidiabetic and lipid-lowering medications was associated with statistically significantly lower adjusted mean ELF (-0.34 [95% CI: -0.47, -0.20] or - 3.2%), FIB-4 (-0.53 [95% CI: -0.74, -0.32] or - 18.0%), APRI (-0.27 [95% CI: -0.37, -0.18] or - 23.1%) and FibroSure/FibroTest scores (-0.08 [95% CI: -0.11, -0.06] or - 14.7%) compared with nonuse. Among participants of European ancestry, the inverse association for FIB-4 (interaction p = 0.01) or APRI (interaction p = 0.004) was stronger in participants with high (>median) versus low (≤median) wPRS; no significant interactions were observed for ELF or FibroSure/FibroTest. CONCLUSIONS: Antidiabetic and lipid-lowering medication use was associated with lower serum liver fibrosis biomarkers. Among participants with European ancestry, associations between combined use of these medications and lower FIB-4 or APRI scores were stronger in those at high genetic risk of MASH. Longitudinal studies are warranted to extend upon these potentially clinically important findings.