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Related Experiment Videos

Association Between SGLT2 Inhibitor Use and Hepatocellular Carcinoma Risk in Type 2 Diabetes: A Systematic Review and

Jing-Hong Hu1,2, Ming-Ling Chang2,3, Tung-Jung Huang1

  • 1Division of Gastroenterology and Hepatology, Yunlin Chang Gung Memorial Hospital, Yunlin County 638, Taiwan.

Biomedicines
|May 27, 2026
PubMed
Summary

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) showed a reduced risk of hepatocellular carcinoma (HCC) in type 2 diabetes patients. However, very low certainty evidence and significant heterogeneity mean these findings are hypothesis-generating, not practice-changing.

Keywords:
SGLT2 inhibitorhepatocellular carcinomameta-analysisobservational studysystematic reviewtype 2 diabetes

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Area of Science:

  • Hepatology and Endocrinology
  • Metabolic Syndrome and Cancer Epidemiology

Background:

  • Type 2 diabetes mellitus (T2DM) is a risk factor for hepatocellular carcinoma (HCC), especially with metabolic dysfunction-associated steatotic liver disease (MASLD).
  • Diabetic hepatocarcinogenesis involves hyperglycemia, insulin resistance, metabolic inflammation, lipotoxicity, oxidative stress, and fibrosis.
  • Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may impact hepatometabolic pathways relevant to HCC development.

Purpose of the Study:

  • To systematically review and meta-analyze observational studies on the association between SGLT2i use and incident HCC risk in adults with T2DM.
  • To assess the epidemiologic evidence linking SGLT2i exposure to HCC risk, considering existing heterogeneity.

Main Methods:

  • Systematic review and meta-analysis of observational studies identified via PubMed, Embase, and Cochrane Library searches up to March 15, 2026.
  • Pooled adjusted time-to-event estimates using a restricted maximum likelihood (REML) random-effects model.
  • Assessed evidence certainty using the GRADE framework, resulting in a 'very low' rating.

Main Results:

  • Six studies with 526,446 participants indicated SGLT2i use was associated with a lower observed HCC risk (pooled HR 0.59; 95% CI 0.45-0.77).
  • Substantial between-study heterogeneity was observed (I² = 75.2%).
  • The 95% prediction interval crossed the null (0.25-1.37), suggesting future studies may not find a protective association.

Conclusions:

  • SGLT2i use was associated with reduced observed HCC risk in available observational data.
  • Very low certainty of evidence, significant heterogeneity, and potential residual confounding preclude causal interpretation.
  • Findings are hypothesis-generating, requiring further validation in hepatology-focused research.