SGLT2 inhibitors reduce HCC risk in T2DM patients with CHB

Christina Lau
18 May 2023
SGLT2 inhibitors reduce HCC risk in T2DM patients with CHB

The use of sodium-glucose cotransporter 2 (SGLT2) inhibitors is associated with a reduced risk of incident hepatocellular carcinoma (HCC) in patients with coexisting type 2 diabetes mellitus (T2DM) and chronic hepatitis B (CHB), a territory-wide cohort study in Hong Kong has shown.


Notably, this protective effect was consistently observed among SGLT2 inhibitor users vs nonusers regardless of sex, age, level of glycaemic control, T2DM duration, presence of hepatic steatosis or cirrhosis, timing of nucleos(t)ide analogue (NA) therapy with respect to baseline, and background use of dipeptidyl peptidase-4 (DPP4) inhibitors, insulin or glitazones. [Hepatology 2023;doi:10.1097/HEP.0000000000000404]


In this real-world population-based study, researchers from the University of Hong Kong identified 14,638 eligible patients (age, 20–85 years; comorbid T2DM and CHB in 2015–2020) from the Hospital Authority’s electronic medical record database. Patients with T2DM and CHB were identified based on prescription records of oral antidiabetic drugs and NAs, respectively.


After propensity score matching, 2,000 patients (1,000 SGLT2 inhibitor users and 1,000 nonusers) were included for analysis. The patients (mean age, 60.9 years; male, 71.3 percent; mean BMI, 26.2 kg/m2) had longstanding T2DM (mean duration, 12.6 years) and mean HbA1c of 8.5 percent, and the majority were on metformin (87.3 percent) and sulphonylureas (64.5 percent). In addition, most patients were on entecavir (82.8 percent) for CHB treatment. Among those on NAs, mean treatment duration was 59.5 months. Hepatic steatosis was present in 56.5 percent vs 52.4 percent of SGLT2 inhibitor users vs nonusers, while cirrhosis was present in 24.3 percent of the overall cohort. Empagliflozin was the most commonly used SGLT2 inhibitor (65.1 percent), followed by dapagliflozin (34.7 percent).


After a median follow-up of 17 months, patients who received SGLT2 inhibitors were found to have a significantly lower risk of incident HCC vs those who did not (incidence rate, 1.39 vs 2.52 cases/100 person-years; hazard ratio [HR], 0.54; 95 percent confidence interval [CI], 0.33–0.88; p=0.013).


“The association remained consistent when stratified by sex [HR, 0.48 (95 percent CI, 0.28–0.83) for male vs HR, 0.94 (95 percent CI, 0.30–2.91) for female], age below or ≥65 years [HR, 0.70 (95 percent CI, 0.37–1.30) vs HR, 0.38 (95 percent CI, 0.17–0.83)], HbA1c below or ≥7.5 percent [HR, 0.44 (0.12–1.59) vs HR, 0.52 (95 percent CI, 0.30–0.87)], diabetes duration below or ≥10 years [HR, 0.24 (95 percent CI, 0.08–0.72) vs HR, 0.71 (95 percent CI, 0.41–1.24)], presence or absence of cirrhosis at baseline [HR, 0.48 (95 percent CI, 0.21–1.12) vs HR, 0.55 (95 percent CI, 0.30–1.00)], presence or absence of steatosis at baseline [HR, 0.58 (95 percent CI, 0.17–1.99) vs HR, 0.92 (95 percent CI, 0.33–2.55)], whether NAs were already in use at baseline or initiated during the observation period [HR, 0.49 (95 percent CI, 0.26–0.92) vs HR, 0.65 (95 percent CI, 0.30–1.38)], and baseline use vs nonuse of DPP4 inhibitors [HR, 0.48 (95 percent CI, 0.24–0.95) vs HR, 0.60 (95 percent CI, 0.30–1.18)], insulin [HR, 0.84 (95 percent CI, 0.43–1.64) vs HR, 0.35 (95 percent CI, 0.17–0.72)], and glitazones [HR, not applicable due to only 1 HCC event in the SGLT2 inhibitor group vs HR, 0.64 (95 percent CI, 0.38–1.06)] [all pinteraction>0.05],” the researchers reported.


“Our current findings provided clinical evidence to support preclinical observations and demonstrated that SGLT2 inhibitor use was associated with a reduced risk of incident HCC in patients with coexisting T2DM and CHB – a clinically relevant study population at high risk of developing HCC,” they noted, adding that this potential additional benefit of SGLT2 inhibitors beyond cardiorenal protection requires validation and confirmation in further studies.

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