From kidney to liver: Are sodium-glucose cotransporter-2 inhibitors emerging as metabolic disease modifiers?
Abstract
Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are increasingly recognized for benefits beyond glycaemic control, with established roles in renal and cardiovascular protection. In diabetic kidney disease (DKD), dapagliflozin-based strategies target persistent proteinuria, while emerging data suggest potential effects on hepatic outcomes, including hepatocellular carcinoma (HCC), in metabolic dysfunction-associated steatotic liver disease (MASLD).
Aim: To evaluate the association between SGLT2 inhibitor use and HCC incidence in MASLD.
Methods: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD1003646). Studies including adults with MASLD comparing SGLT2 inhibitors with other oral hypoglycemic agents and reporting HCC incidence were identified through searches of PubMed, EMBASE, Scopus, and Web of Science up to April 12, 2025. Pooled risk ratios (RRs) were calculated using a random-effects model, and heterogeneity was assessed using the I 2 statistic.
Results: Three retrospective cohort studies comprising 352890 individuals with MASLD were included. SGLT2 inhibitor use was associated with a significantly lower risk of HCC (RR = 0.60, 95%CI: 0.52-0.70; P I 2 = 14.1%). Sensitivity analyses yielded consistent results.
Conclusion: SGLT2 inhibitor use is associated with a reduced incidence of HCC in MASLD, although findings are derived from observational data. These results, together with established…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 352,890 participants or records.
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