Effectiveness of sodium–glucose cotransporter 2 inhibitors in patients with metabolic dysfunction-associated steatotic liver disease: systematic review and meta-analysis of randomized controlled trials

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and can progress to cirrhosis and hepatocellular carcinoma. Treatment options are still lacking. We assessed the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in MASLD. An updated systematic review and meta-analysis of randomized controlled trials in PubMed, Embase, and Cochrane comparing SGLT2i with placebo or active drugs were conducted. Primary outcomes were controlled attenuation parameter (CAP) and liver stiffness by elastography, and fibrosis-4 (FIB-4) score; secondary outcomes were liver enzymes, metabolic and anthropometric measures, and MRI-PDFF. A subgroup without diabetes mellitus (DM) was analyzed. Twenty-nine randomized clinical trials were included (n = 2443). SGLT2i use significantly reduced liver stiffness [mean difference (MD): -0.47 kPa; 95% confidence interval (CI): -0.88 to -0.07; P = 0.022; I2=75%], CAP (MD: -12.24 dB/m; 95% CI: -20.12 to -4.35; P = 0.002; I2=1%), and FIB-4 (MD: -0.22; 95% CI: -0.38 to -0.06; P = 0.008; I2=84%). Improvements were consistently observed in liver enzymes, including alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase. In addition, reductions were noted in body weight, visceral adipose tissue, waist circumference, glycated hemoglobin, and homeostatic model assessment of insulin resistance. In the subgroup analysis of patients without DM (n = 257), SGLT2i also significantly reduced aspartate aminotransferase and gamma-glutamyl transferase, as well as anthropometric parameters. SGLT2i improves hepatic, metabolic, and anthropometric parameters in MASLD, including liver stiffness, steatosis, and FIB-4; benefits also occur in non-DM individuals, warranting further trials.