Gut Liver. 2025;19(5):758-769.

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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제1저자 고윤미, 허문행 · 교신저자 김윤준

PMID 40675923 PMC12436050 DOI 10.5009/gnl240616 IF 4.1 소화기내과

소속 (1)

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Abstract

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.

Keywords

Diabetes mellitusDipeptidyl-peptidase IV inhibitorsFatty liverSodium-glucose transporter 2 inhibitorstype 2

Figures

**Fig. 1** Patient flow diagram. A total of 3,493 eligible DM-MASLD-H patients were included, and they were categorized into the DPP-4i or SGLT-2i group. DM, diabetes mellitus; MASLD-H, metabolic dysfunction-associated steatotic liver disease (HSI plus imaging); HSI, hepatic steatosis index; DPP-4i, dipeptidyl peptidase-4 inhibitor; SGLT-2i, sodium-glucose cotransporter-2 inhibitor.

**Fig. 2** Mean percentage changes in the HSI after 1 year and 3 years of antidiabetic agent treatment in patients with DM-MASLD. Mean percentage changes in the HSI in the DM-MASLD-H group (A, B) and DM-MASLD-I group (C, D). Both groups were balanced using propensity score matching. Data are presented as the mean±SD. DM, diabetes mellitus; MASLD, metabolic dysfunction-associated steatotic liver disease; MASLD-H, MASLD (HSI plus imaging); MASLD-I, MASLD (imaging); HSI, hepatic steatosis index; DPP-4i, dipeptidyl peptidase-4 inhibitor; SGLT-2i, sodium-glucose cotransporter-2 inhibitor.

**Fig. 3** Mean percentage changes in the FIB-4 index after 1 year and 3 years of antidiabetic agent treatment in patients with DM-MASLD. Mean percentage changes in the FIB-4 index in the DM-MASLD-H group (A, B) and DM-MASLD-I group (C, D). Both groups were balanced using propensity score matching. Data are presented as the mean±SD. DM, diabetes mellitus; MASLD, metabolic dysfunction-associated steatotic liver disease; MASLD-H, MASLD (HSI plus imaging); MASLD-I, MASLD (imaging); HSI, hepatic steatosis index; DPP-4i, dipeptidyl peptidase-4 inhibitor; SGLT-2i, sodium-glucose cotransporter-2 inhibitor; FIB-4 index, fibrosis-4 index.

**Fig. 4** Cumulative incidence of liver cirrhosis-related outcomes in patients with DM-MASLD-H (A, B) and DM-MASLD-I (C, D) before and after propensity score matching. DM, diabetes mellitus; MASLD, metabolic dysfunction-associated steatotic liver disease; MASLD-H, MASLD (HSI plus imaging); MASLD-I, MASLD (imaging); HSI, hepatic steatosis index; DPP-4i, dipeptidyl peptidase-4 inhibitor; SGLT-2i, sodium-glucose cotransporter-2 inhibitor.

**Fig. 5** Cumulative incidence of liver-related outcomes in patients with DM-MASLD-H (A, B) and DM-MASLD-I (C, D) before and after propensity score matching. DM, diabetes mellitus; MASLD, metabolic dysfunction-associated steatotic liver disease; MASLD-H, MASLD (HSI plus imaging); MASLD-I, MASLD (imaging); HSI, hepatic steatosis index; DPP-4i, dipeptidyl peptidase-4 inhibitor; SGLT-2i, sodium-glucose cotransporter-2 inhibitor.

그림 출처: PubMed Central 공개 논문 (PMC12436050)

Conflict of interest statement

CONFLICTS OF INTEREST . Y.B.L. has received research grants from Samjin Pharmaceutical Co., Ltd. and Yuhan Corporation. J.H.L. has received research grants from Yuhan Corporation and GC Cell, and lecture fees from GC Cell, Daewoong Pharmaceutical Co., Ltd., and Gilead Sciences Korea Ltd. S.J.Y. has received research grants from Yuhan Corporation and Daewoong Pharmaceutical Co., Ltd. J.H.Y. has received research grants from Bayer AG, Daewoong Pharmaceutical Co., Ltd., and Bukwang Pharmaceutical Co., Ltd. Y.J.K. has received research grants from Roche Ltd., JW CreaGene Inc., Bukwang Pharmaceutical Co., Ltd., Handok Inc., Hanmi Pharm. Co., Ltd., Bristol-Myers Squibb Company, Yuhan Corporation, and PharmaKing Co., Ltd., and lecture fees from Bayer AG, Gilead Sciences Korea Ltd., MSD Korea Ltd., Yuhan Corporation, Samil Pharmaceutical Co., Ltd., CJ Pharmaceuticals, Bukwang Pharmaceutical Co., Ltd., and Handok Inc. S.J.Y. and Y.J.K. are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. All other authors declare no conflicts of interest. No other potential conflicts of interest relevant to this article were reported.

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