Empagliflozin versus sitagliptin for ameliorating intrahepatic lipid content and tissue‐specific insulin sensitivity in patients with early‐stage type 2 diabetes with non‐alcoholic fatty liver disease: A prospective randomized study

Abstract Aim To compare the effects of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors and dipeptidyl peptidase‐4 inhibitors on ectopic fat accumulation and tissue‐specific insulin sensitivity. Materials and Methods This randomized controlled trial enrolled 44 patients with type 2 diabetes (T2D) and non‐alcoholic fatty liver disease (NAFLD). They were randomly assigned to receive either empagliflozin 10 mg/day or sitagliptin 100 mg/day for 12 weeks. The primary endpoint was the change in intrahepatic lipid content (IHL) measured using proton magnetic resonance spectroscopy ( 1 H‐MRS). The secondary endpoints included intramuscular and extramuscular lipid content seen in 1 H‐MRS, body composition seen through dual‐energy X‐ray absorptiometry and tissue‐specific insulin sensitivity shown through hyperinsulinaemic‐euglycaemic clamp using stable isotopic glucose. Liver biopsy samples were pathologically evaluated at baseline. Results At baseline, the mean duration of diabetes, HbA1c level and IHL were 3.7 years, 7.2% and 20.9%, respectively. The median NAFLD activity score was 3.0. IHL was significantly more decreased in the empagliflozin group than that in the sitagliptin group (between‐group difference was −5.2% ± 1.1% and −1.9% ± 1.2%, respectively, (95% confidence interval); −3.3 (−6.5, −0.1), P = .044). However, there were no significant between‐group differences in the change of insulin sensitivity in the liver, muscle or adipose tissues. Interestingly, hepatic insulin sensitivity was significantly increased only in the empagliflozin group and was significantly negatively associated with the change in IHL. Conclusions Empagliflozin significantly improves hepatic steatosis compared with sitagliptin, and this may protect against subsequent hepatic insulin resistance. Early administration of SGLT2 inhibitors is preferable for T2D patients with NAFLD.