Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Non-Alcoholic Fatty Liver Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Non-alcoholic fatty liver disease is the most common form of chronic liver disease. However, effective pharmacotherapy is still lacking. Sodium-glucose cotransporter-2 inhibitors have been proven to improve non-alcoholic fatty liver disease in previous clinical trials. In this work, an updated systematic review and meta-analysis of randomized controlled trials were performed to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with non-alcoholic fatty liver disease. A literature search of PubMed, Cochrane, Web of Science, Medline, and Embase was performed up to August 2024. Articles were sieved to determine eligible randomized controlled trials. Review Manager version 5.4 software was used to conduct the meta-analysis. A total of 21 randomized controlled trials with 1,311 participants were included. Compared with the controls, sodium-glucose cotransporter-2 inhibitor treatment significantly improved the controlled attenuation parameter, liver fat content, liver-to-spleen ratio, liver stiffness measurement, fibrosis-4 index, serum type IV collagen 7S level, serum alanine transaminase level, serum aspartate transaminase level, serum gamma-glutamyl transaminase level, fasting serum insulin level, homeostatic model assessment for insulin resistance, body weight, body mass index, visceral adipose tissue, and subcutaneous adipose tissue. The incidence of total adverse events was not significantly different between the sodium-glucose cotransporter-2 inhibition group and the control group. Sodium-glucose cotransporter-2 inhibitors can improve liver steatosis, liver fibrosis, liver enzymes, insulin resistance, and body composition in patients with non-alcoholic fatty liver disease. Sodium-glucose cotransporter-2 inhibitors are safe and well tolerated. Sodium-glucose cotransporter-2 inhibitors may become promising drugs for non-alcoholic fatty liver disease treatment.