Comparative Efficacy of Oral Antidiabetic Drugs on Metabolic Dysfunction-Associated Steatotic Liver Disease (MΑSLD) Progression in Type 2 Diabetes: A Retrospective Cohort Study

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MΑSLD) is highly prevalent among patients with type 2 diabetes mellitus (T2D), exacerbating the risk of severe hepatic and cardiovascular complications. While metformin remains the first-line therapy, the optimal second-line oral antidiabetic drug (OAD) for mitigating liver disease progression remains unclear. Patients and Methods: This retrospective observational study (2019–2023) evaluated 250 patients with T2D and MΑSLD (defined by a Fatty Liver Index [FLI] > 60) treated at the Outpatient Clinics of 2nd University Department of Internal Medicine of University General Hospital of Alexandroupolis (Greece). Patients were on baseline metformin and initiated one of four OAD classes: Sodium-glucose cotransporter-2 inhibitors (SGLT2i, n=72), Thiazolidinediones (TZDs, n=36), Dipeptidyl peptidase-4 inhibitors (DPP-4i, n=77), or Sulfonylureas (SU, n=65). The primary endpoint was MΑSLD regression (FLI < 30). The secondary endpoint encompassed severe liver-related outcomes and mortality. Results: SGLT2 inhibitors demonstrated the highest probability of MΑSLD regression compared to sulfonylureas (adjusted sub-distribution hazard ratio [aSHR] 1.99; 95% CI, 1.75-2.27), DPP-4 inhibitors (aSHR 1.45; 95% CI, 1.30-1.62), and TZDs (aSHR 1.40; 95% CI, 1.12-1.75). Furthermore, SGLT2i significantly reduced the risk of severe liver-related outcomes compared to sulfonylureas (aSHR 0.37; 95% CI, 0.17-0.82). Conclusions: In patients with T2D and MΑSLD, the addition of SGLT2 inhibitors to metformin significantly promotes fatty liver regression and protects against severe liver-related outcomes compared to other standard OAD classes.