Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, particularly in patients with type 2 diabetes (T2D). The IMAGIN Study, a single-center prospective observational trial, investigated the impact of empagliflozin as an add-on to metformin versus metformin monotherapy on MASLD progression in SGLT2 inhibitor-naïve T2D patients with an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m². The study aimed to assess changes in liver steatosis, fibrosis, and metabolic parameters, alongside exploring potential microRNA (miRNA) biomarkers for treatment response.
Eighty-eight patients were enrolled, with 47 continuing metformin monotherapy (control group) and 41 receiving empagliflozin plus metformin (combination therapy). Assessments, including FibroScan® with controlled attenuation parameter (CAP), liver stiffness measurement, biochemical tests, and anthropometric evaluations, were conducted at baseline, 6 months, and 12 months. At 12 months, the combination therapy group exhibited significantly greater reductions in body mass index (BMI), alanine aminotransferase (ALT), glycated hemoglobin (HbA1c), CAP, and liver stiffness compared to the control group (p < 0.05). Combination therapy was associated with higher odds of steatosis improvement (OR 9.79, p < 0.001) and fibrosis improvement (OR 5.31, p = 0.001), indicating a robust effect on MASLD progression.
Notably, changes in BMI and HbA1c did not correlate with improvements in CAP or liver stiffness, suggesting that empagliflozin’s benefits on liver outcomes may involve mechanisms beyond glycemic control and weight loss. An exploratory analysis of miRNA expression in a subset of 17 patients revealed moderate negative correlations between baseline miR-122 levels and steatosis improvement (r = -0.4820, p = 0.050) and between miR-21 levels and fibrosis improvement (r = -0.5410, p = 0.014), suggesting these miRNAs as potential predictive biomarkers.
The IMAGIN Study demonstrates that empagliflozin as an add-on to metformin significantly enhances liver-related and metabolic outcomes in T2D patients with MASLD compared to metformin alone. However, the study’s single-center design and small sample size for miRNA analysis necessitate larger, multicenter trials to validate these findings and establish miR-122 and miR-21 as reliable biomarkers for MASLD treatment response.
Source: https://www.nmcd-journal.com/article/S0939-4753(25)00438-7/abstract
