SAT-668 Saroglitazar Improves Hepatic Steatosis And Liver Enzymes In Women With PCOS And MASLD: Results Of Evidences VII Randomized Control Study

Abstract Disclosure: D. Parmar: None. N. Samala: Novo Nordisk. J. González-González: None. M. Sarkar: GlaxoSmithKline, Gilead sciences. M. Murthy: None. T. Momin: None. S.R. Joshi: None. S. Krishnan: None. F. Shaikh: None. N. Chalasani: Madrigal, Zydus, Altimmune, Ipsen, Biomed Fusion, GlaxoSmithKline, Pfizer, Inc., Akero, Boston Pharmaceuticals, Exact Sciences, Boehringer Ingelheim. Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in polycystic ovary syndrome (PCOS) and is associated with more severe histology. Therapies specifically focusing on MASLD in PCOS patients are lacking. We therefore investigated the efficacy and safety of saroglitazar 4 mg/day in women with PCOS and MASLD. Methods: EVIDENCES VII (NCT03617263) was a multicenter, randomized, double-blind, placebo-controlled trial of saroglitazar 4mg/day for 24 weeks in women with PCOS and MASLD. The primary end point was a change in MRI-PDFF at 24 weeks from baseline in the per-protocol population (PPP) which included individuals who had an evaluable MRI PDFF at both baseline and at end of treatment. Several prespecified secondary and exploratory efficacy, safety, and tolerability end points were evaluated. Results: Sixty women with PCOS and MASLD meeting predefined eligibility criteria were randomized to receive either 4 mg saroglitazar (n=30) or placebo (n=30). The PPP consisted of 25 saroglitazar and 23 placebo participants with baseline MRI-PDFF (mean ± SD) of 22.02% ± 8.24% and 22.66% ± 9.47%, respectively. Two groups were well matched except for higher HbA1C in the saroglitazar group (5.9% vs 5.5%, p=0.035). MRI-PDFF absolute change from baseline (CFB) to 24 weeks was -3.13 (± 5.35) with saroglitazar vs -0.40 ± 4.98 with placebo (p=0.061). The % CFB of MRI-PDFF at 24 weeks was -14.67 ± 27.77 with saroglitazar vs 1.89 ± 27.47 with placebo (p=0.041). The effect of saroglitazar was more pronounced after adjustment for baseline HbA1c for both absolute CFB (-3.89 ± 0.90 vs 0.41 ± 0.95, p=0.002) and %CFB (-18.9 ± 4.83 vs 6.43 ± 5.04, p<0.001) in MRI-PDFF. The proportion with ≥30% reduction in MRI-PDFF was significantly higher with saroglitazar than placebo (36% vs 8.7%, p=0.024) and mean %CFB favored saroglitazar for ALT (-37% vs 4.8%, p=0.007), AlkP (-28% vs -2.1%, p<0.001), triglyceride (-16% vs 18%, p=0.009), total cholesterol (-13% vs -1.5%, p<0.001), LDL-c (-14.7% vs -3.52, p=0.06), and sdLDL-C (-21% vs 1.4%, p=0.027). There were no significant changes by treatment for HOMA-IR, sex hormone binding globulin, free androgen index, or other sex hormones. Saroglitazar was well tolerated with no differences in body weight, waist circumference or adverse events between the treatment groups. Conclusion: In patients with PCOS and MASLD, saroglitazar 4mg/day significantly improved hepatic steatosis, liver enzymes, and dyslipidemia. Presentation: Saturday, July 12, 2025