Association Between SGLT2 Inhibitor Use and Reduced Risk of Liver-Related Events, Including Hepatocellular Carcinoma, in Diabetic Patients with Viral Hepatitis: A Nationwide Cohort Study

<b>Background and Aims</b>: Diabetes mellitus and chronic hepatitis B/C infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC). This study aimed to evaluate whether sodium-glucose cotransporter-2 inhibitors (SGLT2i) improved liver-related outcomes in patients with chronic viral hepatitis and co-existing diabetes. <b>Methods</b>: Using data from the Korean nationwide cohort, this study included 37,629 patients with concurrent diabetes and chronic hepatitis B/C infection, without prior HCC, who were treated with oral hypoglycemic agents. Patients who were treated with SGLT2is for over 90 days were allocated to the SGLT2i group, whereas those who never received SGLT2is comprised the non-SGLT2i group. The primary outcome was the occurrence of liver-related events, including HCC. <b>Results</b>: After 1:2 propensity score matching, the SGLT2i group comprised 12,543 patients (chronic hepatitis B, CHB: <i>n</i> = 9392; chronic hepatitis C, CHC: <i>n</i> = 4300, CHB & CHC: <i>n</i> = 1149), while the non-SGLT2i group included 25,086 patients (CHB: <i>n</i> = 18,806; CHC: <i>n</i> = 8553, CHB & CHC: 2273). The incidence rate of composite liver-related complications was lower in the SGLT2i group than that in the non-SGLT2i group (6.67 per 1000 vs. 8.99 per 1000). Moreover, SGLT2i therapy was associated with a reduced risk of HCC development (subdistribution hazard ratio [sHR] = 0.77, 95% confidence interval [CI] = 0.66-0.91; <i>p</i> = 0.002) and developing cirrhosis (sHR = 0.67, 95% CI = 0.54-0.83; <i>p</i> < 0.001). <b>Conclusions</b>: SGLT2is should be considered a therapeutic option for controlling diabetes, reducing the metabolic burden, and improving liver outcomes in patients with concurrent diabetes and chronic viral hepatitis.