Comparison of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter-2 Inhibitors in Diabetic Patients with Steatotic Liver Disease.

Background/aims: There is currently insufficient evidence to recommend one oral hypoglycemic agent over another for diabetic patients to reduce hepatic steatosis or prevent advanced fibrosis. We aimed to evaluate the efficacy of dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes mellitus (DM) and metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: This study included diabetic patients with steatotic liver disease who newly received either a DPP-4i or an SGLT-2i as a second-line treatment between 2014 and 2021 at a single tertiary hospital. MASLD was categorized as MASLD-H (radiologic steatosis with a hepatic steatosis index [HSI]>36) or MASLD-I (radiologic steatosis only). Changes in the HSI and fibrosis-4 (FIB-4) index were compared at 1 and 3 years after treatment initiation.

Results: A total of 3,493 patients were consecutively enrolled, with 3,001 receiving DPP-4i treatment and 492 receiving SGLT-2i treatment. After applying propensity score matching, the SGLT-2i group showed a significantly greater reduction in the HSI than the DPP-4i group in the DM-MASLD population at both 1 year (DM-MASLD-H: DPP-4i vs SGLT-2i, -1.4% vs -3.7%, p<0.001; DM-MASLD-I: -1.3% vs -3.8%, p<0.001) and 3 years (DM-MASLD-H: -2.0% vs -4.0%, p=0.001; DM-MASLD-I: -2.4% vs -4.2, p=0.025). The FIB-4 indices of both groups increased; however, the increase at year 1 was more significant in the DPP-4i than in the SGLT-2i group (DM-MASLD-H: 11.4% vs 5.2%, p<0.001; DM-MASLD-I: 10.7% vs 4.3%, p=0.014).

Conclusions: In patients with DM-MASLD, SGLT-2i treatment was associated with a greater reduction in hepatic steatosis and delayed fibrotic progression than DPP-4i treatment.