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The correlation between novel antidiabetic agents utilization and hepatocellular carcinoma incidence in type 2

Junjie Lin1, Tianshu Ren1, Qingchun Zhao1

  • 1Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110016, China.

European Journal of Clinical Pharmacology
|August 11, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) show promise in reducing liver cancer (HCC) and related conditions in type 2 diabetes patients. These antidiabetic drugs offer significant hepatoprotective benefits.

Area of Science:

  • Endocrinology
  • Hepatology
  • Oncology

Background:

  • Type 2 diabetes (T2D) significantly elevates the risk of hepatocellular carcinoma (HCC).
  • Investigating the hepatoprotective potential of antidiabetic medications is crucial for managing T2D complications.
  • Existing research highlights the need for comparative analysis of novel antidiabetic agents' effects on HCC incidence.

Purpose of the Study:

  • To conduct a network meta-analysis evaluating the association between novel antidiabetic agents and HCC incidence in T2D patients.
  • To compare the efficacy of various antidiabetic drug classes in mitigating HCC and other hepatic-related outcomes.
  • To provide evidence-based recommendations for antidiabetic drug selection in T2D patients at risk for HCC.

Main Methods:

  • A systematic network meta-analysis was performed following PRISMA guidelines and a PROSPERO-registered protocol (CRD420251068833).
  • Comprehensive literature searches were conducted across major databases (PubMed, Web of Science, Cochrane Library, Embase, Medline) up to June 6, 2025.
  • Data from 28 cohort studies encompassing 18,212,739 participants with T2D were analyzed for outcomes including HCC incidence, hepatic cirrhosis, hepatic metabolic dysfunction, and all-cause mortality.

Main Results:

  • Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated the greatest effectiveness in reducing HCC incidence.
  • SGLT-2i and glucagon-like peptide-1 receptor agonists (GLP-1 RA) were most effective in decreasing hepatic cirrhosis incidence.
  • For hepatic metabolic dysfunction, SGLT-2i, GLP-1 RA, and DPP4 inhibitors showed decreasing efficacy, while GLP-1 RA ranked highest for reducing all-cause mortality. No publication bias was detected.

Conclusions:

  • SGLT-2 inhibitors and GLP-1 receptor agonists emerge as potentially preferred agents for T2D patients to mitigate HCC incidence and other hepatic complications.
  • These findings suggest significant hepatoprotective effects associated with SGLT-2i and GLP-1 RA in the T2D population.
  • Further research is warranted to elucidate the mechanisms underlying these observed benefits and confirm clinical recommendations.
Keywords:
DPP4 inhibitorsGLP-1 receptor agonistHepatocellular CarcinomaSGLT-2 inhibitorsType 2 Diabetes

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