Impact of empagliflozin as add-on to metformin vs metformin continuation on MASLD progression in type 2 diabetes: The IMAGIN Study

Abstract

Background and aim: MASLD is the leading cause of chronic liver disease. This study evaluated the effects of empagliflozin + metformin (combination therapy) versus metformin monotherapy (control) on MASLD progression in type 2 diabetes (T2D) patients.

Methods and results: This single-center, prospective observational study included SGLT2i-naïve adults with metformin-treated T2D, eGFR ≥45 mL/min/1.73 m², and MASLD. FibroScan®/CAP, biochemical, and anthropometric assessments were conducted at baseline, 6 months, and 12 months. Eighty-eight patients were enrolled (47 controls, 41 combination therapy). At 12 months, combination therapy led to significantly greater improvements in BMI, ALT, HbA1c, CAP, and liver stiffness (p < 0.05). It was associated with higher odds of steatosis (OR 9.79, p < 0.001) and fibrosis improvement (OR 5.31, p = 0.001). Changes in BMI and HbA1c did not correlate with CAP or liver stiffness improvement. Exploratory miRNA analysis (n = 17) suggested potential moderate negative correlations between baseline miR-122 and steatosis improvement (r = -0.4820, p = 0.050) and miR-21 and fibrosis improvement (r = -0.5410, p = 0.014).

Conclusions: Empagliflozin + metformin improved liver parameters more effectively than metformin alone in T2D patients with MASLD. Baseline miR-122 and miR-21 may serve as potential biomarkers for steatosis and fibrosis improvement, respectively.

Keywords: Combination therapy; Empagliflozin; Liver stiffness; MASLD progression; Metformin; Type 2 diabetes.