Comparative effectiveness of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on liver function in patients with type 2 diabetes in Japan: A real-world data analysis

Diabetes Obes Metab. 2024 Mar;26(3):997-1007. doi: 10.1111/dom.15399. Epub 2023 Dec 12.

Abstract

Aim: To compare the effects of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) on liver function in patients with type 2 diabetes (T2D) in Japan.

Materials and methods: This was a Japanese retrospective cohort study using the RWD Database (1 January 2015 to 24 September 2021). Patients newly treated with an SGLT2i or a DPP4i were matched 1:4 (SGLT2i:DPP4i) using propensity score. The primary endpoint was the change from baseline to 1 year after the index date in alanine aminotransferase (ALT). Secondary endpoints included change from baseline in various laboratory test results, including the Fibrosis-4 (FIB-4) index, aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), albumin and HbA1c. Endpoints were compared between treatment groups using Welch's t-test in the full population and in subgroups stratified by baseline characteristics.

Results: Baseline characteristics of 955 and 3063 matched patients newly treated with an SGLT2i and a DPP4i, respectively, were well balanced. Patients receiving an SGLT2i had significantly greater reductions in ALT, FIB-4 index and GGT and a significantly greater increase in albumin than patients receiving a DPP4i. A significantly greater change from baseline in ALT was observed in the SGLT2i group than in the DPP4i group among subgroups with lower baseline FIB-4 index and HbA1c.

Conclusions: In this study, improvements in various measures, including ALT, the FIB-4 index, GGT and albumin, were observed with SGLT2is compared with DPP4is, suggesting that SGLT2is may provide hepatoprotective benefits, including the prevention of liver fibrosis, in patients with T2D in Japan.

Keywords: DPP4 inhibitor; SGLT2 inhibitor; fatty disease; liver; real-world evidence; type 2 diabetes.

Publication types

  • Comparative Study

MeSH terms

  • Albumins
  • Data Analysis
  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Glucose
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Japan / epidemiology
  • Liver
  • Retrospective Studies
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Symporters*

Substances

  • Albumins
  • Dipeptidyl-Peptidase IV Inhibitors
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Glucose
  • Glycated Hemoglobin
  • Hypoglycemic Agents
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors
  • Symporters

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