Impact of Dapagliflozin on Kidney Function Decline in Chronic Kidney Disease Patients: A Systematic Review

This systematic review aimed to evaluate the impact of dapagliflozin therapy on the progression of chronic kidney disease (CKD) in individuals with CKD.

A comprehensive search for randomized controlled trials (RCTs) concerning dapagliflozin was conducted across multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, and Google Scholar, from their inception until January 10, 2025. Of 2,806 identified studies, 15 trials met the inclusion criteria. Upon careful assessment to avoid overlapping populations, 11 publications derived from the Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) parent trial were excluded, leaving four unique independent trials for narrative synthesis. Due to substantial heterogeneity (I² > 90%) and the limited number of studies, meta-analysis was not performed and findings are presented narratively.

A total of 15 articles were identified, 11 were secondary analyses of the DAPA-CKD trial (NCT03036150) reporting on the same 4,304 participants. Following exclusion of overlapping publications, four unique trials remained. The findings for eGFR decline were highly variable across studies, ranging from a mean difference of -6.60 mL/min/1.73m² (Cherney et al., 2020) to +0.93 mL/min/1.73m² (Heerspink et al., 2020). Substantial heterogeneity (I² = 93.7%) precluded meaningful meta-analysis. For composite renal outcomes, only one unique trial reported this outcome, preventing quantitative synthesis.

While the effect of Dapagliflozin on eGFR decline was inconclusive due to substantial heterogeneity, the available evidence from the DAPA-CKD trial suggests a reduction in the risk of adverse clinical renal outcomes. However, the limited number of independent trials and considerable heterogeneity underscore the need for more standardized RCTs. Overall, dapagliflozin appears to confer renal protective benefits and is considered safe for patients with CKD.