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.

Oct 28, 2025Diabetes, obesity & metabolism

How New Diabetes Medications Affect Kidney Health

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Abstract

Dapagliflozin 10 mg demonstrated 55% reduced risk in composite renal outcomes compared to placebo in patients with type 2 diabetes and chronic kidney disease.

SGLT-2 inhibitors consistently provided renal protection, particularly dapagliflozin and canagliflozin.
Canagliflozin significantly reduced urinary albumin-to-creatinine ratio, while dapagliflozin had no effect on this measure.
No significant changes in estimated glomerular filtration rate (eGFR) were observed with any of the antidiabetic agents.
The certainty of evidence was high for comparisons against placebo but varied for indirect estimates.
DPP-4 inhibitors did not show any renal benefits in this patient population.

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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.

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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.

Abstract

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