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Background Metabolic Associated Fatty Liver Disease (MAFLD) is highly prevalent among individuals with type 2 diabetes mellitus (T2DM), yet no specific pharmacological therapy has been approved. Sodium-glucose co-transporter-2 inhibitors (SGLT2i), including luseogliflozin, have demonstrated potential hepatometabolic benefits.Methods This study evaluated the impact of luseogliflozin on hepatic steatosis and fibrosis in T2DM patients with MAFLD using biochemical and imaging assessments over 6 months. In a prospective, double-blinded, randomized controlled trial, 60 adults with T2DM and MAFLD were randomized to receive either luseogliflozin (5 mg daily) plus standard therapy or standard therapy alone. Diet and physical activity were stabilized. Biochemical markers (HbA1c, AST, ALT, lipid profile, Fib-4 index) were assessed at baseline, 3, and 6 months. Hepatic steatosis was graded via ultrasound, and fibrosis by shear wave elastography (SWE). Fifty-five participants completed the study (Luseogliflozin n = 27; Conventional n = 28). Outcomes were analyzed using paired t-tests and categorical comparisons.Results The luseogliflozin group demonstrated significant improvements in FIB-4 index (2.24±0.79 to 1.30±0.75 at 6 months, P<0.001), whereas conventional therapy showed no significant change (2.41±1.61 to 2.18±1.76). HbA1c improved markedly with luseogliflozin (9.9±2.04% to 8.4±1.64%, P<0.001) but not in the conventional group. AST decreased significantly with luseogliflozin (41.4 to 29.3 U/L, P<0.001), with no change in controls. Between-group differences at 3 and 6 months were significant for FIB-4, HbA1c, and AST (P<0.01). ALT and triglyceride reductions were not statistically significant. Cholesterol showed a modest, non-significant reduction with luseogliflozin but increased in controls.Imaging findings supported clinical improvements. Ultrasound revealed increased Grade 0 steatosis from 44.4% to 55.5% with luseogliflozin, versus a decline from 46.4% to 39.9% in controls. No progression to Grade 3 occurred in either group. SWE demonstrated increased F0–F1 fibrosis from 44.4% to 59.2% with luseogliflozin, while controls declined from 32.1% to 25.0%. No patients progressed to F4 with luseogliflozin, whereas one control remained at F4. (IDDF2026-ABS-0196 Table 1)Conclusions Luseogliflozin added to standard therapy improved liver fibrosis scores, glycemic control, and liver enzymes in MAFLD patients with T2DM. Ultrasound and SWE confirmed a reduction in hepatic steatosis and fibrosis progression. Larger, longer-term trials with histological endpoints are warranted.Abstract IDDF2026-ABS-0196 Table 1Biochemical and imaging outcomes at 3,6 monthsLuseogliflozin vs Conventional Therapy – Clinical Outcomes at 3 & 6 MonthsMean ± SD · Between-group P values shown · Significant values (P < 0.05) highlightedParametersLuseogliflozin Group(n = 27)Conventional Group(n = 28)P Value Baseline2.24 ± 0.72.41 ± 1.610.611 At 3 months1.56 ± 0.752.88 ± 2.260.006*Fibrosis-4 Index Score1.3 ± 0.752.18 ± 1.760.017* At 6 months-0.9 ± 0.62 (P<0.001)-0.09 ± 0.5 (P=0.178)- Change from baseline Baseline9.9 ± 2.048.31 ± 1.540.002* At 3 months8.66 ± 1.698.39 ± 1.930.585HbA1c (%)8.4 ± 1.648.4 ± 1.60.476 At 6 months-1.5 ± 0.85 (P<0.001)0.08 ± 1.6 (P=0.354)-Change from baseline Baseline41.41 ± 19.1642.50 ± 16.610.822 At 3 months29.81 ± 42.9342.39 ± 15.520.001*AST (Units/L)29.3 ± 17.138.7 ± 13.40.004* At 6 months-12.27 ± 15 (P<0.001)-3.96 ± 14.2 (P=0.17)- Change from baseline Baseline42.52 ± 30.2842.86 ± 23.520.963 At 3 months34.15 ± 19.5137.04 ± 23.110.619ALT (Units/L)33.86 ± 26.331.7 ± 16.10.384 At 6 months-5.34 ± 21.3 (P=0.107)-7.7 ± 22(P=0.9)- Change from baseline Baseline4.55 ± 0.944.63 ± 1.120.779 At 3 months4.15 ± 0.814.87 ± 1.370.012*Total Cholesterol (mmol/L)4.28 ± 1.144.72 ± 1.30.016* At 6 months-0.25 ± 0.9 (P=0.09)0.23 ± 1.06 (P=0.14)- Change from baseline Baseline1.85 ± 1.361.41 ± 0.710.103 At 3 monthsTriglyceride (mmol/L)1.51 ± 0.551.68 ± 1.130.474 At 6 months1.7 ± 1.351.44 ± 0.850.154 Change from baseline-0.13 ± 1.2 (P=0.28)0.27 ± 0.57 (P=0.4)-*P < 0.05 – statistically significant between-group difference · Values presented as Mean ± SD · Within-group P values shown in parentheses