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Association of Sodium-Glucose Cotransporter-2 Inhibitors With Reduced Hepatocellular Carcinoma Risk in Patients With

Jonggi Choi1,2,3, Vy H Nguyen4, Eric Przybyszewski2,3

  • 1Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

The American Journal of Gastroenterology
|December 16, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) show reduced hepatocellular carcinoma (HCC) risk in type 2 diabetes mellitus (T2DM) patients. This finding supports SGLT2is as a potential chemopreventive therapy for HCC in T2DM.

Area of Science:

  • Endocrinology
  • Hepatology
  • Oncology

Background:

  • Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are common type 2 diabetes mellitus (T2DM) treatments.
  • Potential hepatoprotective effects of SGLT2is warrant investigation for liver cancer risk.

Purpose of the Study:

  • To evaluate the association between SGLT2 inhibitor use and hepatocellular carcinoma (HCC) risk.
  • To compare HCC risk among T2DM patients initiating SGLT2i versus other antidiabetic medications.

Main Methods:

  • Retrospective cohort study utilizing electronic health records from US and Korean medical centers (2013-2024).
  • Included adults with T2DM initiating SGLT2i, DPP4i, GLP-1RA, or sulfonylureas.
  • Used 6-month landmark analysis and inverse probability weighting with Fine-Gray competing risk models.

Main Results:

  • SGLT2i use was linked to significantly lower HCC risk compared to sulfonylureas (SHR 0.44) and DPP4 inhibitors (SHR 0.53).
  • HCC risk was comparable between SGLT2i and GLP-1RA users (SHR 0.87).
  • Protective effects were consistent across subgroups, including younger patients, males, and those with chronic liver disease.

Conclusions:

  • SGLT2 inhibitor therapy is associated with a reduced risk of HCC in T2DM patients.
  • Findings suggest a potential chemopreventive role for SGLT2 inhibitors against HCC.
Keywords:
SGLT2 inhibitorchemopreventionhepatic decompensationhepatocellular carcinomatype 2 diabetes mellitus

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