Society of Diabetic Nephropathy Prevention Journal of Nephropharmacology 2345-4202 16 2 2027 07 01 Assessing liver function and its correlation with various anti-diabetic medications: a biomarker-driven analysis of the hepatorenal protection axis e12766 e12766 10.34172/npj.2026.12766 EN Shaimaa Saleh Khudhur https://orcid.org/0000-0003-0559-1228 Noor Mohammed Abdulrahman https://orcid.org/0000-0002-0208-9227 Qutaiba A. Qasim https://orcid.org/0000-0001-9566-0850 Journal Article 10.34172/npj.2026.12766 2025 03 02 2025 10 22 Introduction: Chronic renal failure and diabetes mellitus commonly coexist, with each disorder adversely affecting the other’s development. Liver function had a significant role in metabolic regulation and drug metabolism, affecting both glycemic control and renal outcomes. Objectives: This investigation aimed to investigate liver function and its relationship with various anti-diabetic medicines by a biomarker-driven approach to better identify hepatorenal protection. Patients and Methods: This cross-sectional study, conducted from October 2024 to January 2025 in Basra Governorate, Iraq. This study analyzed 250 diabetic individuals to assess hepatic biomarker profiles through anti-diabetic regimens. Diabetic individuals were classified into five groups; those who administered metformin only, the engaged populations who exclusively used sulfonylurea and cases who were taking dipeptidyl peptidase-4 inhibitors (DPP-4i), SGLT-2i (sodium-glucose co-transporter 2 inhibitors), and combination therapy. In this study levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin were assessed. Results: This study indicated that, values of the ALT, AST, ALP, and bilirubin in people on sulfonylurea were significantly higher in comparison with individuals who were under the treatments of metformin, DPP-4 inhibitors, SGLT-2 inhibitors, or mix therapies. Patients, who received metformin, DPP-4 inhibitor, SGLT-2 inhibitor, and combination therapy, in their turn, did not differ in downstream metabolites of the liver and their concentrations, as they all displayed similar values of these liver enzymes and bilirubin. Conclusion: We found that the administration of sulfonylurea is highly correlated with the occurrence of a significantly high level of liver functions test (ALT, AST, ALP, and bilirubin) as compared to metformin, DPP-4 inhibitors, SGLT-2 inhibitors and combination therapies, which bore the same hepatic profile. Our results demonstrated that liver safety should be evaluated in the administration of anti-diabetic drugs and particularly in cases with preexisting liver problems or prone to liver toxicity.