Sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation and hepatocellular carcinoma prognosis

Abstract

Introduction Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. Emerging findings from laboratory studies indicate that SGLT2 inhibitors can improve liver function and suppress the proliferation of hepatocellular carcinoma (HCC) cells. The aim of this study was to test the hypothesis that initiation of SGLT2 inhibitors improves HCC prognosis in a human population. Methods We used National Surveillance, Epidemiology and End Results (SEER)—Medicare linked data in the United States to evaluate the role of SGLT2 inhibitor initiation on the survival of HCC patients. 3,185 HCC patients newly diagnosed between 2014 and 2017 aged 66 years or older with pre-existing type 2 diabetes were included and followed to the end of 2019. Information on SGLT2 inhibitor initiation was extracted from the Medicare Part D file. Results SGLT2 inhibitor initiation was associated with significantly lower mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.54–0.86) with stronger association for longer duration of use (HR = 0.60, 95% CI = 0.41–0.88). Further, we found that SGLT2 inhibitor initiation was associated with a lower risk mortality risk ranging from 14% to 60% regardless of patient demographic variables, tumor characteristics, and cancer treatments. Conclusion Our large SEER-Medicare linked data study indicates that SGLT2 inhibitor initiation was associated with improved overall survival of HCC patients with pre-existing type 2 diabetes compared with no SGLT2 inhibitor use. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.

SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong

“…Indeed, among individuals with HCC, a recent study demonstrated that the use of SGLT2i was also associated with a better prognosis 55 . Several mechanisms have been proposed in preclinical studies.…”

“…Indeed, among individuals with HCC, a recent study demonstrated that the use of SGLT2i was also associated with a better prognosis. [55] Several mechanisms have been proposed in preclinical studies. First, SGLT2i may directly inhibit the growth and proliferation of HCC cells through suppression of glucose uptake and glycolysis.…”

Letter to the Editor: Novel antidiabetic drugs and the risk for HCC. What else to expect from these “wonderful” drug classes?

“…Of note, concurrent use of metformin provided an additional mortality benefit versus SGLT-2 inhibitor use alone 2. This study suggested that even among patients with a definite diagnosis of HCC, initiation of SGLT-2 inhibitor might improve overall mortality, if the patient is eligible for this drug class 2…”

“…Of note, concurrent use of metformin provided an additional mortality benefit versus SGLT-2 inhibitor use alone. [2] This study suggested that even among patients with a definite diagnosis of HCC, initiation of SGLT-2 inhibitor might improve overall mortality, if the patient is eligible for this drug class. [2] It is also known that patients with NAFLD and type 2 diabetes mellitus may progress to advanced liver fibrosis and finally cirrhosis, while for those with established cirrhosis there is an increased risk for HCC.…”

“…Recent epidemiologic data are highly supportive of the beneficial effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on mortality among subjects with an established diagnosis of HCC and type 2 diabetes mellitus2; SGLT-2 inhibitors provided a significant decrease in the risk for HCC-related death by 32%, with duration of use more than a year resulting in a significant reduction in the corresponding risk by 40%. Of note, concurrent use of metformin provided an additional mortality benefit versus SGLT-2 inhibitor use alone 2. This study suggested that even among patients with a definite diagnosis of HCC, initiation of SGLT-2 inhibitor might improve overall mortality, if the patient is eligible for this drug class 2…”