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

Abstract

Background and AimSodium 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).MethodsA 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.ResultThe 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.ConclusionThis 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.

Efficacy and safety of oral semaglutide in patients with non‐alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study

“…In general, lifestyle modifications for weight reduction and treatment of extrahepatic comorbidities take precedence over direct NAFLD treatment. 8 , 9 , 10 Recently, anti‐diabetic drugs, such as glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) 11 , 12 , 13 and sodium/glucose cotransporter 2 inhibitors (SGLT2‐Is), 14 , 15 , 16 , 17 , 18 , 19 , 20 have been investigated as effective drugs for NAFLD treatment.…”

The Potential of SGLT-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: The Current Status and Future Perspectives

“…GLP-1RAs reduce body weight, regulate the menstrual cycle, and improve hyperandrogenism even better than metformin, but they are disadvantaged due to the need for subcutaneous administration [ 36 ]. The proven effect of GLP-1RAs and SGLT-2is on metabolic processes may suggest they are suitable for the treatment of dyslipidemia, NAFLD, obstructive sleep apnea, and PCOS [ 37 , 38 ].…”

MASLD treatment—a shift in the paradigm is imminent

“…Another class of anti-diabetics, sodium-glucose cotransporter-2 inhibitors (SGLT-2i) may also be of benefit, even though studies with strong endpoints including liver biopsy are lacking. Treatment with SGLT-2i drugs, such as empagliflozin, seems to induce mild weight loss, as well as important reductions in liver fat content (over 20% relative decrease) and might decrease the risk of fibrosis progression according to small studies with NIT’s assessment of liver fibrosis ( 142 , 143 ). Importantly, SGLT-2i have important cardiorenal protective effects, being associated with overall and cardiovascular mortality ( 144–147 ).…”