LAUSR

BACKGROUND AND AIMS Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of hepatocellular carcinoma (HCC). Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB. APPROACH AND RESULTS Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity-score for their demographics, biochemistry results, liver-related characteristics and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p=0.013). The association remained similar regardless of sex, age, glycaemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background anti-diabetic agents including dipeptidyl peptidase-4 inhibitors, insulin or glitazones (all p-interaction>0.05). CONCLUSIONS Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC.