BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of hepatocellular carcinoma (HCC). Research on the hepatoprotective effects of antidiabetic agents is ongoing. This study aimed to investigate the correlation between novel antidiabetic agents and HCC incidence in T2D patients through a network meta-analysis.
METHODS: The study followed a predefined PROSPERO-registered protocol (CRD420251068833) and reported results per the PRISMA extension for network meta-analysis. Databases such as PubMed, Web of Science, Cochrane Library, Embase, and Medline were searched from their inception to June 6, 2025. Eligible studies involved patients aged ≥ 18 with T2D, covering various antidiabetic drugs. Data extraction used standardized tables, with primary and secondary outcomes including HCC incidence, hepatic cirrhosis, hepatic metabolic dysfunction, and all-cause mortality.
RESULTS: A total of 5,018 citations were retrieved, with 28 cohort studies involving 18,212,739 participants meeting the inclusion criteria. No inconsistency was found among outcome studies. SGLT-2 inhibitors (SGLT-2i) were most effective in reducing HCC incidence. In secondary outcome analysis, SGLT-2i and Glucagon-like peptide-1 receptor agonist (GLP-1 RA) were most effective for reducing hepatic cirrhosis incidence. For hepatic metabolic dysfunction, SGLT-2i, GLP-1 RA, and DPP4i ranked from most to least effective. For all-cause mortality, GLP-1 RA ranked highest. No publication bias was detected.
CONCLUSION: This network meta-analysis indicates that SGLT-2i and GLP-1 RA may be preferred for T2D patients to reduce HCC incidence and other hepatic-related outcomes. Further research is needed to confirm these findings and explore the underlying mechanisms.
SYSTEMATIC REVIEW REGISTRATION: CRD420251068833.
