Saroglitazar improves hepatic steatosis and liver enzymes in women with polycystic ovary syndrome and MASLD: A multicenter, double-blind, placebo-controlled study

Background and Aims: Polycystic ovary syndrome (PCOS) is the leading endocrine disorder in reproductive-age women. MASLD is common in women with PCOS, but they are underrepresented in MASLD therapeutic trials. We evaluated the safety and efficacy of saroglitazar, a novel PPARα/γ agonist, on hepatic steatosis, in women with PCOS and MASLD. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase 2A trial, 60 women (18-45 y) with PCOS and MASLD were randomized 1:1 to either saroglitazar 4 mg or placebo for 24 weeks. The primary endpoint was relative (percent) change in hepatic fat content (HFC), measured by MRI proton-density fat-fraction (PDFF). Primary analysis was performed in the per-protocol population (saroglitazar: 25; placebo: 23). Results: Participants in the saroglitazar group showed a significant reduction in percent HFC at 24 weeks from baseline compared to placebo ([LS Means±SE]: −14.81±5.52 vs. 1.96±5.75, P =0.041). When controlled for baseline HbA1c imbalance, the beneficial effect of saroglitazar was more pronounced ([LS Mean±SE]: −18.93±4.83 vs. 6.43±5.04, P <0.009). Higher proportion in the saroglitazar group achieved ≥30% reduction in MRI-PDFF (36.0% vs. 8.7%; P =0.025). Saroglitazar also significantly reduced aminotransferase, lipid parameters and FAST TM score. Adverse events (AE) were comparable between the groups, none serious. One pregnancy in saroglitazar arm had uneventful maternal and neonatal outcomes. Conclusion: In women with PCOS and MASLD, saroglitazar significantly improved hepatic steatosis, liver enzymes, lipid profile, and FAST TM score. These findings support further evaluation of saroglitazar in larger studies in women with PCOS. Trial Registration: ClinicalTrials.gov: NCT03617263