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Life sciences · Journal article
Diabetology International · October 31, 2026
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Background. 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.Methods. 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.Results. 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.Conclusions. 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.Graphical abstract. Supplementary information. The online version contains supplementary material available at https://doi.org/10.1007/s13340-026-00941-2.