SGLT2 inhibitors in diabetic biopsy proven MASH patients: A systematic review and meta-analysis

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as Non-alcoholic steatohepatitis (NASH), is a progressive inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD). It is associated with increased risk of cirrhosis, hepatocellular carcinoma (HCC), and other extrahepatic complications. While sodium glucose co-transporter 2 inhibitors (SGLT2i) have been evaluated in MASLD through several meta-analyses, their specific role in biopsy-proven MASH remains understudied. This meta-analysis aimed to evaluate the efficacy and safety of SGLT2i in diabetic patients with biopsy-proven MASH.

Literature databases, including Medline through PubMed, Scopus, Cochrane, Google Scholar, Web of Science, and ClinicalTrials.gov, were searched for relevant studies in May 2025. A Single arm meta-analysis was performed using the random effects model using the standardized mean change score (SMCR) as a measure of effect size.

Seven trials with a total of 110 patients in the single intervention arms were included. Pooled analysis indicated a significant within-group improvement from baseline in liver enzymes, controlled attenuation parameter (CAP) [SMCR of -0.56 (95% CI: -0.75 to -0.36)], liver stiffness measurement (LSM) [SMCR of -0.58 (95% CI: -1.03 to -0.14)], biopsy NAFLD Activity Score (NAS) [SMCR of -1.18 (95% CI: -2.29 to -0.06)], steatosis, ballooning, and fibrosis by liver biopsy, waist circumference [SMCR of -0.33 (95% CI: -0.49 to -0.17], ferritin, and systolic blood pressure (P < 0.05) following SGLT2i administration. Heterogeneity varied across outcomes with minimal to low heterogeneity for liver enzymes, CAP, anthropometric measures and glycemic markers; indicating a consistent effect across studies; whereas substantial heterogeneity was observed for LSM, triglycerides and histological outcomes. SGLT2i were well-tolerated across studies, showing a consistent safety profile.

SGLT2i significantly improved hepatic, metabolic, cardiometabolic risk, and most histological parameters; compared to baseline. SGLT2i might be a potential clinical therapeutic strategy for patients with biopsy-proven MASH, particularly those with concurrent type II DM. Owing to the limited certainty of evidence and heterogeneity among studies, these findings should be interpreted cautiously.