Anti-Diabetic Medications for Type 2 Diabetics with Non-Alcoholic Fatty Liver Disease. Evidence from a Network Meta-Analysis of Randomised Controlled Trials.

ABSTRACT Objective Type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD) are closely related, and anti-diabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of anti-diabetic agents for the treatment of NAFLD in patients with T2DM. Methods Medline and Embase were searched for randomised controlled trials relating to the use of antidiabetic agents including sodium-glucose transport protein 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin on its on NAFLD in patients with diabetes. The p score was used as a surrogate marker of effectiveness. Results A total of 14 articles were included in the analysis. PPARγ agonists was ranked as the best treatment in steatosis reduction. PPARγ agonists resulted in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists (MD: -6.02%, CI: -10.37% to -1.67%) and SGLT2i (MD: -2.60%, CI: -4.87% to -0.33%) compared to standard of care for reduction of steatosis. Compared to PPARγ agonists, SGLT2i resulted in a statistical significant reduction in fibrosis (MD: -0.06, CI: -0.10 to -0.02). BMI reduction was highest in SGLT2i and GLP1-RA. Additionally, SGLT2i was ranked as the best treatment in increasing HDL and reducing LDL. Conclusion GLP-1RA and SGLT2i were found to be suitable alternatives for the treatment of NAFLD in diabetics with reduction in BMI, fibrosis, and steatosis. SGLT2i were also found to have the added benefit of lipid modulation.