Lower Risks of New-Onset Hepatocellular Carcinoma in Patients With Type 2 Diabetes Mellitus Treated With SGLT2 Inhibitors Versus DPP4 Inhibitors

Jun 11, 2024Journal of the National Comprehensive Cancer Network : JNCCN

Lower risk of new liver cancer in type 2 diabetes patients treated with SGLT2 inhibitors compared to DPP4 inhibitors

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Abstract

Of the 62,699 patients analyzed, 0.37% developed hepatocellular carcinoma (HCC), with 36 cases in the SGLT2i group and 130 cases in the DPP4i group.

SGLT2i use was associated with a lower risk of HCC compared to DPP4i, with a hazard ratio of 0.42.
In patients with cirrhosis or advanced fibrosis, the risk of developing HCC was significantly lower for SGLT2i users (hazard ratio of 0.12).
SGLT2i usage also showed a reduced risk of HCC in individuals with hepatitis B virus (HBV) infection (hazard ratio of 0.32) and hepatitis C virus (HCV) infection (hazard ratio of 0.41).
The association between SGLT2i and lower HCC risk remained consistent across various risk models and analyses.

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BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i.

METHODS: This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors.

RESULTS: A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses.

CONCLUSIONS: SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.

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Lower Risks of New-Onset Hepatocellular Carcinoma in Patients With Type 2 Diabetes Mellitus Treated With SGLT2 Inhibitors Versus DPP4 Inhibitors

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