Luseogliflozin improves liver fat deposition in type 2 diabetes patients with nafld compared with metformin: A prospective, randomized, controlled pilot study

Background and Aim: Although nonalcoholic fatty liver disease (NAFLD) is a risk factor for many conditions including liver cirrhosis, hepatocellular carcinoma, and cardiovascular events, there are few effective treatments beyond weight loss. Recently, SGLT2 inhibitors, used in diabetes management, have been reported to improve visceral adiposity and to induce weight loss. These effects may also improve liver fat deposition. We investigated the effect of luseogliflozin on liver fat deposition compared to metformin, in type 2 diabetes patients with NAFLD. Materials and Methods: This study was a prospective randomized controlled pilot study. A total of 32 type 2 diabetes patients with NAFLD diagnosed by abdominal sonography were recruited. Participants were randomly assigned to receive either luseogliflozin (2.5 mg, newly administrated; n=16; L group) or metformin (500 mg, newly or additionally administrated; n=16; M group). The primary objective was to compare the change in liver-to-spleen attenuation ratio (ΔL/S), measured by computed tomography (CT), between both groups. The secondary objective was to compare changes in visceral fat mass area (ΔVFA), measured by CT, as well as changes in body mass index (ΔBMI) and HbA1c (ΔHbA1c) between both groups. Data were collected at baseline and after 6 months. Results: The ΔL/S significantly improved in the L group compared with the M group (ΔL/S: 0.18 (-0.09, 0.19) vs. -0.12 (-0.20, 0.19), p<0.01). The ΔVFA, ΔHbA1c, and ΔBMI significantly improved in the L group compared to the M group (median = -11.9 cm2, interquartile range = (-31.3,-4.4) vs. 3.6 cm2 (-6. 9,10.1), p = 0.02; -0.8% (-1.3,-0.1) vs. -0.1% (-0.4, 0.1), p = 0.03; -0.76 kg/m2 (-0.91, -0.32) vs. -0.11 kg/m2 (-0.55, 0.15), p = 0.01; respectively). Conclusion: This study showed that luseogliflozin significantly reduced liver fat deposits compared to metformin.