Systematic review and meta-analysis of the association between the use of SGLT2 inhibitors and hepatocellular carcinoma

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly recognized for their potential role beyond glycemic control, particularly in the context of hepatocellular carcinoma (HCC). This systematic review and meta-analysis aims to evaluate the association between SGLT2 inhibitor use and the incidence or prognosis of HCC, drawing on emerging evidence that suggests these agents may improve liver function and reduce cancer cell proliferation. Materials and Methods: This investigation was executed in accordance with the PRISMA guidelines, employing a systematic review and meta-analysis methodology. In this investigation, the databases ProQuest, PubMed, Embase, Web of Science, Cochrane, as well as the Google Scholar search engine, were scrutinized until August 25, 2024. The analysis of the data was conducted utilizing STATA 14 software, with the threshold for statistical significance established at P<0.05. Results: In seven reviewed studies, 422,174 individuals were evaluated, and the results indicated that there was no significant association between the use of SGLT2i and HCC (HR: 0.65; 95% CI: 0.41, 1.01). However, SGLT2i use reduced the risk of HCC by 36% compared to dipeptidyl peptidase-4 inhibitors (DPP4) and by 73% compared to beta blockers. The use of SGLT2i decreased the risk of HCC in women (56%) and men (55%). In Asia, there was no significant relationship between SGLT2i use and HCC (HR: 0.57; 95% CI: 0.27, 1.16), while in Europe and the Americas, it reduced the risk of HCC by 22% and 32%, respectively. Among patients aged 50 to 59 years, there was no significant association between SGLT2i use and HCC (HR: 0.89; 95% CI: 0.63, 1.25), but in those aged 60 to 69 years, SGLT2i use resulted in a 62% reduction in HCC risk. There was no significant association between SGLT2i use and liver cirrhosis (HR: 0.98; 95% CI: 0.76, 1.26). Conclusion: In conclusion, while the overall analysis reveals no significant association between SGLT2 inhibitor use and HCC, the findings suggest a noteworthy reduction in HCC risk compared to other treatments, particularly in older adults and across different regions. These results highlight the potential benefits of SGLT2 inhibitors in mitigating HCC risk, warranting further investigation to clarify their role in liver cancer prevention. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (ID: CRD42024593426) and Research Registry (UIN: reviewregistry1888) websites.