Efficacy of SGLT2 Inhibitors Versus GLP-1 Receptor Agonists in Type 2 Diabetes Patients with Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Abstract

Our meta-analysis aimed to compare the efficacy of GLP-1RAs and SGLT2is in improving hepatic and metabolic outcomes in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. We sought to determine which drug class offers superior benefits in liver enzyme reduction, glycemic control, and lipid metabolism. Recent meta-analyses and observational studies support substantial cardiorenal, metabolic, and hepatic benefits from GLP-1RAs and SGLT2is in T2DM patients. Large trials show that angiocrine and neuroprotective mechanisms may contribute to benefits beyond glycemic control. Combination therapy with GLP-1RA + SGLT2i is associated with additive reductions in major adverse cardiovascular events, heart failure hospitalization, and serious renal events compared to monotherapy. Cardiometabolic data from US cohorts suggest lower risks of myocardial infarction and stroke when a newer-generation GLP-1RA is added to SGLT2i therapy. Subgroup meta-analyses confirm cardiovascular risk reduction regardless of baseline metformin use. Distinct patterns emerge: GLP-1RAs are particularly effective for stroke prevention, weight loss, and glycemic control, while SGLT2is excel in preventing heart failure, cardiovascular mortality, and renal progression . 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.