Anti-inflammatory versus metabolic therapy in MASLD: a randomized clinical trial of aspirin and dapagliflozin using fibroscan outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major hepatic consequence of metabolic dysfunction, yet evidence-based pharmacologic options remain limited. Repurposing widely available agents with metabolic and anti-inflammatory actions may offer a clinically meaningful benefit. To compare the effects of aspirin and dapagliflozin on hepatic steatosis, fibrosis, liver enzymes, and lipid profile in patients with MASLD. In this prospective randomized interventional study, 80 adults with confirmed MASLD were allocated (1:1) to aspirin 100 mg once daily or dapagliflozin 10 mg once daily for 6 months (n = 40 per group). Baseline and 6-month measurements included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglycerides, high-density lipoprotein cholesterol (HDL-C), total cholesterol, and FibroScan-derived parameters, including controlled attenuation parameter (CAP; dB/m), which quantifies hepatic steatosis, and liver stiffness measurement (LSM; kPa), a surrogate marker of liver fibrosis. The primary endpoints included the between-group differences in changes in LSM, CAP, liver enzymes, and lipid profile from baseline to 6 months. Ethics approval was obtained (FMBSUREC/04032025). The trial was registered at ClinicalTrials.gov (NCT07338331) on 20 Dec 2025. Dapagliflozin significantly improved hepatic steatosis, reflected by lower CAP values compared to aspirin (260.35 ± 20.78 vs 271.48 ± 12.58 dB/m; p = 0.005), and reduced total cholesterol levels (138.87 ± 54.70 vs 192.48 ± 79.46 mg/dL; p = 0.003). In contrast, aspirin demonstrated a greater reduction in liver stiffness (LSM) (6.15 ± 2.55 vs 8.58 ± 4.13 kPa; p = 0.002) and alanine aminotransferase (ALT) percentage change (- 44.54% vs - 17.84%; p = 0.025). Other biochemical parameters showed no statistically significant between-group differences (all p > 0.05). Aspirin and dapagliflozin exert distinct and potentially complementary effects in MASLD, with dapagliflozin preferentially improving hepatic steatosis and aspirin showing a greater impact on fibrosis-related parameters. These findings support a dual-pathway therapeutic model targeting steatosis and fibrosis and underscore the need for larger trials evaluating combined strategies and histological outcomes.