Baseline monocyte SGLT2 mRNA expression and changes in the fibrosis-4 index after luseogliflozin treatment in participants with type 2 diabetes and MASLD

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in type 2 diabetes. We investigated the association between monocyte mRNA expression of sodium-glucose cotransporter 2 (SGLT2), the molecular target of luseogliflozin, and changes in the fibrosis-4 (FIB-4) index during treatment with this agent. This single-center retrospective observational study used prospectively collected peripheral blood monocyte samples from 82 participants with type 2 diabetes and MASLD who had received luseogliflozin for at least 6 months. Baseline monocyte SGLT2 mRNA expression was measured using quantitative real-time polymerase chain reaction. Clinical and laboratory parameters, including FIB-4 index, were evaluated at baseline and 6 months after luseogliflozin initiation. Changes were calculated as the 6-month value minus the baseline value; therefore, negative values indicated reductions. After 6 months, waist circumference, hemoglobin A1c, liver enzyme levels, high-sensitivity C-reactive protein, and the FIB-4 index decreased significantly. Baseline monocyte SGLT2 mRNA expression was negatively correlated with the change in the FIB-4 index, indicating that higher baseline expression was associated with a greater reduction. In multiple regression analyses, natural-log-transformed baseline monocyte SGLT2 mRNA expression remained associated with the change in the FIB-4 index after adjustment for baseline clinical variables. Higher baseline monocyte SGLT2 mRNA expression was associated with a greater reduction in the FIB-4 index after luseogliflozin treatment. This finding should be interpreted as an exploratory association between a cell-specific transcriptomic feature and changes in a fibrosis-related index, rather than as evidence of functional SGLT2 signaling in monocytes or histological fibrosis regression.