Effects of SGLT2 Inhibitor Therapy Combined with a Moderate-Carbohydrate Diet in Patients with MASLD

Background/Objectives: Moderate carbohydrate diets (MCD) and sodium glucose cotransporter 2 inhibitors (SGLT2i) both improve metabolic status and liver injury in metabolic dysfunction-associated steatotic liver disease (MASLD), but the therapeutic effect of their combined use remains unclear. This study evaluated whether adding an SGLT2i to an MCD provides incremental benefit. Methods: Among 327 patients with MASLD, 259 receiving MCD alone were assigned to the control group, and 68 receiving luseogliflozin 2.5 mg/day were assigned to the combination group. Propensity score matching using age, sex, height, weight, body mass index, alanine aminotransferase (ALT), hemoglobin A1c (HbA1c), and fibrosis-4 index identified 53 matched patients per group. Results: The proportion achieving ≥7% weight loss after 1 year was significantly higher in the combination group (74% vs. 26%). Reductions in body fat, visceral fat area, and liver fat content were also greater with combination therapy. ALT normalization rates were similar (64% vs. 55%). No significant between group differences were observed in liver enzymes, shear wave velocity, or Mac 2 binding protein glycosylation isomer levels. Improvements in several metabolic parameters—including triglycerides, uric acid, ferritin, homeostatic model assessment for insulin resistance, and HbA1c—were more pronounced in the combination group. Conclusions: Although adding an SGLT2i to an MCD did not provide additional short-term benefits in liver injury or fibrosis markers, it produced substantially greater reductions in body, visceral, and liver fat and broader metabolic improvements. By facilitating clinically meaningful weight loss, SGLT2i may serve as a valuable adjunct to MCD for MASLD.