Comparative Efficacy of Oral Antidiabetic Drugs on Metabolic Dysfunction-associated Steatotic Liver Disease Progression in Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease is highly prevalent among patients with type 2 diabetes mellitus, exacerbating the risk of severe hepatic and cardiovascular complications. While metformin remains the first-line therapy, the optimal second-line oral antidiabetic drug for mitigating liver disease progression remains unclear.

Patients and methods: This retrospective observational study (2019-2023) evaluated 250 patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (defined by a fatty liver index score of>60) treated at the Outpatient Clinics of the 2^nd University Department of Internal Medicine of University General Hospital of Alexandroupolis (Greece). Patients were on baseline metformin and initiated one of four oral antidiabetic drug classes: sodium-glucose cotransporter-2 inhibitors (n = 72), thiazolidinediones (n=36), dipeptidyl peptidase-4 inhibitors (n=77), and sulfonylureas (n=65). The primary end point was metabolic dysfunction-associated steatotic liver disease regression (a fatty liver index score of<30). The secondary end point encompassed severe liver-related outcomes and mortality.

Results: Sodium-glucose cotransporter-2 inhibitors demonstrated the highest probability of metabolic dysfunction-associated steatotic liver disease regression compared to sulfonylureas (adjusted sub-distribution hazard ratio: 1.99 and 95% confidence interval: 1.75-2.27), dipeptidyl peptidase-4 inhibitors (adjusted sub-distribution hazard ratio: 1.45 and 95% confidence interval: 1.30-1.62), and thiazolidinediones (adjusted sub-distribution hazard ratio: 1.40 and 95% confidence interval: 1.12-1.75). Furthermore, sodium-glucose cotransporter-2 inhibitors significantly reduced the risk of severe liver-related outcomes compared to sulfonylureas (adjusted sub-distribution hazard ratio: 0.37 and 95% confidence interval: 0.17-0.82).

Conclusions: In patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease, the addition of sodium-glucose cotransporter-2 inhibitors to metformin significantly promotes fatty liver regression and protects against severe liver-related outcomes compared to other standard oral antidiabetic drug classes.