Lower risks of sodium glucose cotransporter 2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors for new-onset non-alcoholic fatty liver disease and hepatocellular carcinoma in type 2 diabetes mellitus: A population-based study

BackgroundThe association between sodium glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) and the risks of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are currently unknown. MethodsThis was a retrospective population-based cohort study including type-2 diabetes mellitus (T2DM) patients treated with either SGLT2I or DPP4I between 1st January 2015 and 31st December 2019 in Hong Kong. Patients with concurrent DPP4I and SGLT2I usage were excluded. The primary outcomes were NAFLD and HCC. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) was performed using the nearest neighbour search. Univariable and multivariable Cox regression was applied to identify significant predictors. Competing risks models and multiple approaches using the propensity score were performed. ResultsThis cohort included 62699 patients with T2DM, amongst which 22154 patients were on SGLT2I and 40545 patients were on DPP4I. After matching (44308 patients), 1090 patients developed new-onset NAFLD (Incidence: 4.6; 95% Confidence interval [CI]: 4.3-4.9) and 187 patients developed HCC (Incidence: 0.8; 95% CI: 0.7-0.9). Overall, SGLT2I was associated with lower risks of NAFLD (Hazard ratio [HR]: 0.39; 95% CI: 0.34-0.46), and HCC (HR: 0.46; 95% CI: 0.29-0.72) compared to DPP4I after adjustments. SGLT2I was also associated with lower risks of cancer-related mortality (HR: 0.29; 95% CI: 0.23-0.37) and all-cause mortality (HR: 0.28; 95% CI: 0.25-0.31). However, amongst patients with hepatitis B virus infection, SGLT2I was associated with higher risks of HCC (HR: 3.28; 95% CI: 1.21-8.90). The results were consistent in competing risk models and different matching approaches. ConclusionSGLT2I was associated with lower risks of NAFLD, and HCC compared to DPP4I after propensity scores matching and adjustments. Lay summaryThe association between two antidiabetic medications, SGLT2I and DPP4I, and the risks of fatty liver disease and liver cancer have not been explored. In our study, SGLT2I was associated with a lower risk of fatty liver disease and liver cancer compared to DPP4I amongst patients with type 2 diabetes. However, DPP4I was associated with lower risks of liver cancer compared to SGLT2I among patients with hepatitis B virus infection Central illustration O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/22278847v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1e602feorg.highwire.dtl.DTLVardef@1ce9485org.highwire.dtl.DTLVardef@178c14eorg.highwire.dtl.DTLVardef@db2215_HPS_FORMAT_FIGEXP M_FIG C_FIG