The Emerging Therapeutic Promise of SGLT2 Inhibitors in Metabolic Dysfunction-Associated Steatotic Liver Disease.

OBJECTIVE

This review aims to synthesize preclinical and clinical evidence supporting the therapeutic potential of Sodium-glucose cotransporter 2 inhibitors (SGLT2i) in Metabolic dysfunction-associated steatotic liver disease (MASLD).

METHODS

We conducted a comprehensive literature review. Our analysis encompassed both mechanistic studies and clinical trials to summarize the pharmacologic profile of SGLT2i and the pathophysiological basis of MASLD.

RESULTS

SGLT2i confer multifaceted benefits in MASLD by targeting core pathological processes. They ameliorate hepatic steatosis by promoting fatty acid β-oxidation and inhibiting lipogenesis, improve insulin sensitivity, and attenuate inflammation, oxidative stress, and fibrosis. Additional mechanisms involve gut microbiota modulation and autophagy activation. Clinically, SGLT2i use is associated with reduced liver enzymes, improved histological features, and potentially suppressed hepatocarcinogenesis, with benefits observed in patients with and without type 2 diabetes. Emerging data suggest synergistic effects from SGLT2i-based combination therapies.

CONCLUSIONS

SGLT2i represent a promising, multifaceted therapeutic strategy for MASLD, addressing its metabolic-inflammatory drivers while providing extrahepatic cardiorenal protection. Their repurposing is supported by a favorable safety profile. Future research should focus on long-term outcomes and combination therapy trials to solidify their role in MASLD management.