Comparison of the renal outcomes of novel antidiabetic agents in patients with type 2 diabetes with chronic kidney disease: A systematic review and network meta-analysis of randomized controlled trials.

AIMS: To investigate the renal outcomes of dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose transport protein-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (T2DM) with chronic renal disease (CKD).

MATERIALS AND

METHODS

PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were searched through July 2025 for randomized controlled trials with ≥24 weeks of follow-up in patients with T2DM and CKD. Outcomes included composite renal outcome, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR). A network meta-analysis was conducted, and the certainty of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation used to evaluate evidence certainty (GRADE).

RESULTS

Twenty RCTs enrolling 80,670 participants were included. Compared with placebo, several agents significantly reduced composite renal outcomes, with dapagliflozin 10 mg showing the greatest efficacy (OR 0.55, 95% CI 0.42-0.72; high-certainty evidence), followed by canagliflozin, empagliflozin, efpeglenatide, sotagliflozin 400 mg, semaglutide, and dulaglutide 1.5 mg. Canagliflozin 100-300 mg significantly reduced UACR, whereas dapagliflozin had no effect. None of the novel antidiabetic agents significantly altered eGFR. Certainty of evidence ranged from high for placebo-controlled comparisons to low or very low for indirect estimates.

CONCLUSIONS

In patients with T2DM and CKD, SGLT2 inhibitors provide the most consistent renal protection, while GLP-1 receptor agonists offer additional but variable benefits. Dapagliflozin showed the greatest efficacy, and canagliflozin most strongly reduced albuminuria, highlighting meaningful heterogeneity across agents. DPP-4 inhibitors conferred no renal benefit. Overall, evidence from placebo-controlled trials was robust, whereas certainty was lower for indirect estimates, highlighting the need for drug-specific evaluation in clinical practice.