Efficacy and safety of imeglimin hydrochloride for metabolic dysfunction-associated steatotic liver disease with type 2 diabetes: Single-center, single-arm phase 2 (IMELD study)

Imeglimin, a novel oral antidiabetic agent classified as a glimin, was developed for the treatment of type 2 diabetes (T2D). This single-center, single-arm interventional study evaluated the efficacy and safety of 24-week imeglimin treatment in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and T2D. Patients with MASLD and T2D were treated with imeglimin 1000 mg twice daily for 24 weeks. The primary endpoint was reduction in alanine aminotransferase (ALT) levels from baseline. Secondary endpoints included changes in metabolic parameters (including hemoglobin A1c, homeostatic model assessment of β-cell function, and homeostatic model assessment of insulin resistance), liver-related parameters (including aspartate aminotransferase [AST], gamma-glutamyl transpeptidase, hepatic fat, and fibrosis markers), and body composition. Twenty-five patients were included in the final analysis. As a primary outcome, the median ALT level was significantly reduced, from 56.00 (47.00-75.00) U/L at baseline to 34.00 (29.00-51.00) U/L at 24 weeks (P < .001). AST level and hemoglobin A1c value were also significantly reduced. The fibrosis-4 index showed a significant reduction at 12 weeks. By contrast, no significant changes were observed for gamma-glutamyl transpeptidase, homeostatic model assessment of β-cell function, homeostatic model assessment of insulin resistance, hepatic fat content parameters, other fibrosis-related parameters (excluding fibrosis-4 index), and body composition. All adverse events were grade 1, and no patients discontinued treatment due to adverse events. Imeglimin treatment was associated with improvements in serum ALT and AST levels after 24 weeks in patients with MASLD and T2D. These findings provide preliminary evidence of the potential clinical utility of imeglimin in this population and warrant confirmation in larger randomized controlled studies.