Efficacy of sodium glucose cotransporter 2 inhibitors on hepatic fibrosis and steatosis in non-alcoholic fatty liver disease: an updated systematic review and meta-analysis

Abstract

Abstract Non-alcoholic fatty liver disease (NAFLD) is a substantial contributor to liver-related morbidity worldwide, and yet, there are no standard, universal pharmacologic therapies approved for this indication. The aim of this systematic review and meta-analysis is to evaluate the effectiveness of SGLT-2 inhibitors in improving hepatic steatosis and hepatic fibrosis in patients with NAFLD. An extensive electronic database search was done to identify studies published from inception until December 2023, without any language restrictions. All randomized controlled trials (RCT) that evaluated the use of SGLT-2 inhibitors for patients with NAFLD, regardless of diabetes mellitus status, were included. The Cochrane Risk of Bias 2.0 tool was used to assess the risk of bias of each study included. Evidence from all studies were synthesized as mean differences for continuous data, and as risk ratio for dichotomous outcomes. An inverse variance or Mantel–Haenszel test was used in conjunction with a random-effects meta-analysis model, where necessary. 18 eligible RCTs involving 1330 participants were analyzed, all of which had risk of bias ranging from low to some concerns. Significant difference in means was observed for controlled attenuation parameter (6 trials, n = 372; MD: − 10.59 dB/m, 95% CI [− 18.25, − 2.92], p = 0.007, I2 = 0%); L/S ratio (3 trials, n = 163; MD: 0.11, 95% CI [0.01, 0.21], p = 0.04, I2 = 78%); LSM (7 trials, n = 447; MD: − 0.67 kPa, 95% CI [− 1.19, − 0.16], p = 0.010, I2 = 69%); MRI-PDFF (5 trials, n = 330; MD: − 2.61%, 95% CI [− 5.05, − 0.17], p = 0.04, I2 = 78%), and FIB-4 index (10 trials, n = 648; MD: − 0.12, 95% CI [− 0.21, − 0.04], p = 0.005, I2 = 16%) after SGLT-2 inhibitor treatment as compared to controls. In conclusion, the use of SGLT-2 inhibitors may lead to slight improvement of hepatic steatosis and/or fibrosis as compared to controls in patients with NAFLD and Type 2 diabetes mellitus based on imaging and histopathology biomarkers with low to moderate certainty of evidence.