Meta‐analysis of the effects of sodium glucose cotransporter 2 inhibitors in non‐alcoholic fatty liver disease patients with type 2 diabetes

BACKGROUND AND AIM: Sodium glucose cotransporter 2 inhibitors (SGLT‐2i), by way of their unique mode of action, present an attractive strategy for the treatment of type 2 diabetes and non‐alcoholic fatty liver disease (NAFLD), which often coexist and may lead to severe complications. However, the evidence for treatment with SGLT‐2i is limited to small heterogeneous studies. Therefore, this meta‐analysis was conducted to deduce the effects of SGLT‐2i in NAFLD with type 2 diabetes (T2D). METHODS: A web‐based search identified nine randomized controlled trials from the Cochrane Library, Embase, and PubMed for this meta‐analysis. The Comprehensive Meta‐Analysis Software version 3 was used to calculate the effect size. RESULT: The outcomes of interest were analyzed from a pooled population of 11 369 patients—7281 on SGLT‐2i and 4088 in the control arm. SGLT‐2i therapy produced a statistically significant improvement in alanine aminotransferase [standardised mean difference (SDM), −0.21, 95% confidence interval (CI), −0.32 to −0.10, P < 0.01], aspartate aminotransferase (Standardised mean difference (SDM), −0.15, 95% CI, −0.24 to −0.07, P < 0.01), and liver fat as measured by proton density fat fraction (SDM, −0.98, 95% CI, −1.53 to −0.44, P < 0.01) in comparison to standard of care or placebo. In addition, there was a significant reduction in glycosylated hemoglobin (SDM, −0.37, 95% CI, −0.60 to −0.14, P < 0.01) and weight (SDM, −0.58, 95% CI, −0.93 to −0.23, P < 0.01) in the SGLT‐2i arm. CONCLUSION: This meta‐analysis provides a convincing signal that SGLT‐2i have a salutary effect on NAFLD in type 2 diabetes (T2D), probably driven by an improvement of glycemia and body weight, which in turn attenuates hepatic inflammation and hepatic fat accumulation.