Efficacy of Orlistat on Cardiometabolic Indices in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A GRADE-Assessed Systematic Review and Meta-Analysis of RCTs

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to cardiometabolic abnormalities. Orlistat has demonstrated potential benefits on metabolic parameters, yet its efficacy in MASLD remains unclear. This meta-analysis aimed to assess the effects of Orlistat on cardiometabolic indices in patients with MASLD. To identify relevant randomized controlled trials (RCTs), a comprehensive search was conducted across major databases from inception to January 2026. Outcomes assessed included aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), triglycerides (TG), total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), fasting blood glucose (FBG), fasting insulin (FI), homeostatic model assessment for insulin resistance (HOMA-IR), body mass index (BMI), systolic and diastolic blood pressure (BP). Pooled effect sizes were calculated using a random-effects model using weighted mean differences (WMD) with 95% confidence intervals (CI). Six RCTs were included in this meta-analysis. The pooled analysis showed that Orlistat significantly improved liver enzymes, with reductions in AST (WMD: -4.01 U/L, 95% CI: -6.05 to -1.97, p = 0.005), ALT (WMD: -8.70 U/L, 95% CI: -16.51 to -0.90, p = 0.036), and GGT (WMD: -7.74 U/L, 95% CI: -14.88 to -0.59, p = 0.04). It also improved lipid profile by lowering LDL-C (WMD: -5.61 mg/dL, 95% CI: -7.36 to -3.86, p = 0.002) and increasing HDL-C in long-term interventions (≥24 months, WMD: 1.65 mg/dL, 95% CI: 0.95–2.36, p = 0.02). Glycemic markers improved, with significant reductions in FBS (WMD: -4.05 mg/dL, 95% CI: -6.32 to -1.78, p = 0.005), FI (WMD: -2.50 μU/mL, 95% CI: -3.46 to -1.55, p = 0.003), and HOMA-IR (WMD: -0.70, 95% CI: -0.98 to -0.41, p = 0.004). Orlistat did not significantly affect BP. BMI decreased significantly overall (WMD: -0.99 kg/m², 95% CI: -1.18 to -0.81, p < 0.001), with stronger effects in long-term interventions. Orlistat may improve cardiometabolic and liver function in MASLD patients, significantly reducing liver enzymes, enhancing lipid profiles, improving glycemic control, and lowering BMI. These results indicate its potential as an effective therapeutic option for metabolic management. However, larger, high-quality RCTs with longer follow-up are necessary to confirm its long-term efficacy and safety.