S2463 Targeting Liver and Glucose: Comparative Efficacy of SGLT2i and GLP-1RA in NAFLD Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis

Introduction: Type 2 diabetes mellitus (T2DM) is a global metabolic disorder marked by decreased insulin sensitivity and impaired insulin secretion, resulting in hyperglycaemia. It is frequently associated with non-alcoholic fatty liver disease (NAFLD). Recent studies suggest that SGLT2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists may improve liver enzymes and reduce liver fat in T2DM patients with NAFLD. Methods: This systematic review and meta-analysis was conducted following the PRISMA guidelines. We conducted a comprehensive literature search across 5 electronic databases: (PubMed, Scopus, Ovid, the Cochrane Library, and Web of Science). We included randomized controlled trials (RCTs) evaluating the efficacy of SGLT2 and GLP-1 agonists on NAFLD in T2DM patients. We screened the records to identify eligible studies, extracted and analyzed the data using the meta package (version 4.0.3) in R and STATA MP version 17. We used a random-effects model to calculate the weighted mean difference (WMD) with 95% confidence interval (CI). Heterogeneity was assessed using Cochran’s Q test and the I² statistic. Sensitivity, subgroup, and publication bias analyses were applied. We used both Galbraith and funnel plots to further assess heterogeneity and publication bias. Results: Thirty-seven RCTs, with a total of 2,609 patients, were included in this study. SGLT2i significantly reduced ALT (MD = -8.79, 95% CI: -12.80 to -4.79, P < 0.0001) and aspartate aminotransferase (MD = -10.26, 95% CI: -17.03 to -3.49, P = 0.0030), while GLP-1RA Showed no significant effect on both enzymes. GGT changes were not changed in both groups. Both treatments significant reduction in body weight and BMI. Fasting glucose and HOMA-IR improved in both groups, with a greater reduction in glucose seen in SGLT2i group. GLP-1RA group reduced HbA1c but not in SGLT2i group. No significant changes were observed in total cholesterol, HDL, or LDL. Triglycerides were significantly reduced in both groups, with a greater effect in SGLT2i. Postprandial glucose was reduced significantly with GLP-1RA. Conclusion: Both GLP-1 and SGLT2 showed benefits in patients with NAFLD and T2DM. SGLT2 showed greater effects on liver enzymes, while GLP-1 showed improved weight loss and glycemic control. Still, the choice of treatment should be based on the patient’s goals and the main clinical needs.