Protective Effects of Linagliptin Against Acute Kidney Injury in Animal Models: A Systematic Review and Meta-Analysis

Acute kidney injury (AKI) remains a serious clinical condition associated with high rates of morbidity and mortality, while effective pharmacological treatment options remain limited. This systematic review and meta-analysis examined the effects of linagliptin in experimental models of AKI. The protocol was prospectively registered in PROSPERO (CRD420261399729), and the review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Scopus, Embase via Ovid, and Web of Science were searched from inception through 25 May 2026 to identify controlled in vivo studies evaluating linagliptin in mammalian AKI models. Pooled effect estimates were calculated using random-effects models, and methodological quality was assessed with the SYRCLE risk-of-bias tool. Six studies met the eligibility criteria. Compared with control treatment, linagliptin treatment resulted in significant reductions in serum creatinine, the primary outcome (mean difference [MD] = −1.17 mg/dL, 95% confidence interval −1.94 to −0.39; p = 0.0031; I2 = 94.41%), and blood urea nitrogen (MD = −79.33 mg/dL, 95% CI: −130.38 to −28.27; p = 0.0023; I2 = 99.15%). Changes in cystatin C, kidney injury molecule-1, inflammatory mediators, oxidative-stress indices, and apoptosis-related markers were also reported. However, the considerable heterogeneity indicated substantial variation among studies. Because only six studies were available and most potential subgroups contained one or two studies, reliable subgroup analyses by AKI induction model, animal species, linagliptin dose, or treatment duration could not be performed. Five studies had an unclear overall risk of bias, and publication bias could not be assessed. Therefore, the pooled estimates should be considered exploratory average associations across heterogeneous experimental models rather than uniform treatment effects. Additional rigorously designed preclinical studies are required to determine the reproducibility and translational relevance of these findings.