Mpisa S, Soldera J. From kidney to liver: Are sodium–glucose cotransporter-2 inhibitors emerging as metabolic disease modifiers? World J Nephrol 2026; 15(3): 121652 [DOI: 10.5527/wjn.121652]
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Jonathan Soldera, MSc Acute Medicine and Gastroenterology, University of South Wales in association with Learna Ltd, University of South Wales, Cardiff CF37 1DL, United Kingdom. jonathansoldera@gmail.com
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Urology & Nephrology
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Mpisa S, Soldera J. From kidney to liver: Are sodium–glucose cotransporter-2 inhibitors emerging as metabolic disease modifiers? World J Nephrol 2026; 15(3): 121652 [DOI: 10.5527/wjn.121652]
World J Nephrol. Sep 25, 2026; 15(3): 121652 Published online Sep 25, 2026. doi: 10.5527/wjn.121652
From kidney to liver: Are sodium–glucose cotransporter-2 inhibitors emerging as metabolic disease modifiers?
Jonathan Soldera, Sydney Mpisa
Sydney Mpisa, Jonathan Soldera, MSc Acute Medicine and Gastroenterology, University of South Wales in association with Learna Ltd, University of South Wales, Cardiff CF37 1DL, United Kingdom
Jonathan Soldera, Department of Gastroenterology, Logan Hospital, Brisbane 4101, Queensland, Australia
Author contributions: Soldera J, Mpisa S participated in the concept and design research, drafted the manuscript and contributed to data acquisition, analysis and interpretation; Soldera J contributed to study supervision; all authors contributed to critical revision of the manuscript for important intellectual content.
AI contribution statement: Limited use of artificial intelligence tools was made to assist in language polishing and summarization tasks. However, no part of the manuscript was entirely generated by artificial intelligence; instead, it underwent extensive manual input by the author, rigorous review, and revision. Artificial intelligence tools did not participate in research design, data collection, statistical analysis, or result interpretation. All scientific content, conclusions, and final wording were determined by the author. No artificial intelligence-generated charts, images, or graphic elements were used in the manuscript.
Conflict-of-interest statement: The authors declare to have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Jonathan Soldera, MSc Acute Medicine and Gastroenterology, University of South Wales in association with Learna Ltd, University of South Wales, Cardiff CF37 1DL, United Kingdom. jonathansoldera@gmail.com
Received: March 30, 2026 Revised: April 28, 2026 Accepted: May 21, 2026 Published online: September 25, 2026 Processing time: 137 Days and 2.3 Hours
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 I2 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 < 0.0001), corresponding to an approximate 40% relative risk reduction, with low heterogeneity (I2 = 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 renal and cardiovascular benefits, support a broader role for SGLT2 inhibitors as modifiers of metabolic disease across organ systems.
Core Tip: Sodium-glucose cotransporter-2 inhibitors extend beyond glycaemic control and may modify key pathways of metabolic disease. Evidence from diabetic kidney disease and metabolic dysfunction-associated steatotic liver disease suggests these agents attenuate inflammation and fibrosis, with a potential association with reduced hepatocellular carcinoma incidence. This supports a shift toward integrated, cross-organ metabolic disease modification.
