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

Jul 17, 2025Gut and liver

Comparing Two Diabetes Medicines for Patients with Fatty Liver Disease

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Abstract

A total of 3,493 patients were evaluated for the effects of two diabetes medications on liver health.

SGLT-2 inhibitors resulted in a greater reduction in compared to DPP-4 inhibitors at 1 year and 3 years.
At 1 year, the reduction in the hepatic steatosis index was -3.7% for SGLT-2i versus -1.4% for DPP-4i in patients with radiologic steatosis and -3.8% versus -1.3% in patients with radiologic steatosis only.
At 3 years, reductions were -4.0% for SGLT-2i versus -2.0% for DPP-4i in the steatosis group and -4.2% versus -2.4% in the steatosis-only group.
Both treatment groups experienced an increase in the fibrosis index, with a more significant increase observed in the DPP-4i group at 1 year.
The increase in the fibrosis index at 1 year was 11.4% for DPP-4i compared to 5.2% for SGLT-2i in patients with radiologic steatosis.

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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 [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.

Key numbers

-3.7%

Reduction in Hepatic Steatosis at 1 Year

SGLT-2i vs. DPP-4i in DM-MASLD patients

11.4%

Increase in FIB-4 Index at 1 Year

DPP-4i vs. SGLT-2i in DM-MASLD patients

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

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