Saroglitazar 4 Mg in Metabolic Dysfunction‐Associated Steatotic Liver Disease: 24‐Week Results From Phase 4 Study

BACKGROUND AND AIMS: Saroglitazar magnesium, a dual PPAR α/γ agonist, is approved in India for the treatment of non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD). While controlled trials with saroglitazar have demonstrated improvements in hepatic and metabolic parameters in patients with MASLD, real-world data in populations with diverse metabolic comorbidities remain limited. METHODS: This is an ongoing, prospective, single-arm, multicenter, real-world, phase 4 study evaluating the effectiveness and safety of saroglitazar 4 mg once daily in patients with MASLD. The current interim analysis includes 500 patients who completed 24 weeks of treatment. Changes in liver stiffness measurement (LSM), hepatic steatosis (CAP and UAP), glycemic control, lipid profile, liver enzymes and non-invasive fibrosis scores were assessed. Safety was evaluated based on treatment-emergent adverse events (TEAEs). This was a non-protocol-defined, exploratory interim analysis; all statistical inferences are descriptive and p-values are nominal. RESULTS: and 42% had obesity. After 24 weeks of treatment, mean LSM ± SD decreased from 10.1 ± 3.2 kPa to 8.0 ± 3.2 kPa (-20.7%, p < 0.001) and CAP decreased by 20.3 dB/m (p < 0.001). ALT levels reduced by 33.6% (p < 0.001) and HbA1c by 4.8% (p < 0.001). Improvements were also observed in lipid profile and fibrosis scores (FIB-4, FAST, APRI, ALERT). A total of 68 patients (13.6%) reported TEAEs, the majority of which were mild (85.5%) and unrelated to the study drug. No deaths were reported. CONCLUSIONS: In this interim real-world analysis, saroglitazar 4 mg was associated with improvements in liver stiffness, hepatic steatosis, metabolic parameters and non-invasive fibrosis markers in patients with MASLD. The treatment was generally well tolerated. These findings warrant further confirmation upon completion of the 52-week analysis. IMPACT AND IMPLICATIONS: Saroglitazar 4 mg for 24 weeks was associated with improvements in surrogate markers of liver injury, steatosis, glycaemic control and lipid metabolism, with good tolerability. These interim real-world findings support further evaluation in the planned 52-week analysis. CLINICAL TRIAL NUMBER: CTRI/2023/05/053326 [Registered on: 31/05/2023].