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. Metabolic dysfunction-associated steatotic liver disease (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 peroxisome proliferator-activated receptors α/γ agonist, for the treatment of 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, measured by MRI proton density fat fraction. 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 hepatic fat content at 24 weeks from baseline compared to placebo ([least squares mean±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 ([least squares mean±SE]: -18.93±4.83 vs. 6.43±5.04, p <0.009). A higher proportion in the saroglitazar group achieved ≥30% reduction in magnetic resonance imaging-proton density fat fraction (36.0% vs. 8.7%; p =0.025). Saroglitazar also significantly reduced aminotransferase levels, lipid parameters, and the FibroScan AST score. Adverse events were comparable between the groups, and none were serious. One pregnancy in the saroglitazar arm resulted in uneventful maternal and neonatal outcomes. CONCLUSIONS: In women with PCOS and MASLD, saroglitazar significantly improved hepatic steatosis, liver enzymes, lipid profile, and FibroScan AST score. These findings support further evaluation of saroglitazar in larger studies in women with PCOS.