In a network meta-analysis of 143,296 patients, SGLT2 inhibitors ranked highest for preventing heart failure and kidney decline in diabetic CKD, while GLP-1 receptor agonists excelled at reducing heart attacks, stroke, and albuminuria.
P-score 1.00 for heart failureSGLT2 inhibitors achieved a perfect ranking score for heart failure prevention in diabetic CKD patients, with GLP-1 RAs ranking second
What the researchers found
Across 26 RCTs with 143,296 participants with T2DM and CKD:
- SGLT2 inhibitors ranked highest (by P-score) for: composite renal events (0.94), eGFR decline >40% or renal replacement therapy (0.99), MACE (0.93), and heart failure (1.00)
- GLP-1 RAs ranked highest for: myocardial infarction (0.87), macroalbuminuria (0.86), and stroke (0.83)
- Both SGLT2 inhibitors and GLP-1 RAs had equal P-scores (0.83) for reducing all-cause mortality
- DPP-4 inhibitors had limited benefits compared to either SGLT2 inhibitors or GLP-1 RAs across all outcomes
Why it matters
Diabetic kidney disease is one of the most dangerous metabolic complications, dramatically increasing cardiovascular and renal risks. Clinicians managing these complex patients need to know which drug class to prioritize. This meta-analysis provides the clearest comparative ranking to date, showing that the two drug classes have complementary strengths — supporting the clinical strategy of using SGLT2 inhibitors for renal and heart failure protection while adding GLP-1 peptide agonists for atherosclerotic cardiovascular risk reduction.
How the study worked
Systematic review and network meta-analysis of randomized controlled trials published between 2014-2024, identified through PubMed, Scopus, and clinical trial registries. Twenty-six studies with 143,296 participants with T2DM and CKD were included. Drug classes compared: SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors. P-scores were used to rank treatments for each outcome (higher = better).
What this study cannot tell us
Network meta-analysis relies on indirect comparisons when head-to-head trials are unavailable. The analysis aggregates different drugs within each class (e.g., multiple SGLT2 inhibitors), potentially masking within-class differences. CKD staging and severity varied across included trials. The time period (2014-2024) means the newest GLP-1 agonist data (high-dose semaglutide) and tirzepatide CKD data may not be fully captured. P-scores provide rankings but not absolute effect sizes for comparison.
How to read the evidence
This is a systematic review and network meta-analysis of 26 randomized controlled trials — one of the highest levels of evidence. The large sample (143,296 participants) provides robust statistical power, though the indirect comparison methodology has inherent limitations.
When this study was published
Published in 2025 using trials from 2014-2024, this analysis captures the most comprehensive evidence base for cardiorenal outcomes of diabetes drugs in CKD patients.
The bigger picture
This analysis provides a clear therapeutic hierarchy for managing the cardiorenal complications of diabetic kidney disease. The complementary strengths of SGLT2 inhibitors (kidney and heart failure) and GLP-1 peptide agonists (atherosclerotic events) support the emerging consensus for combination therapy. The poor showing of DPP-4 inhibitors — despite being the most widely prescribed class in some markets — may accelerate the shift toward the more effective (and more expensive) drug classes.
Questions still open
- Does combination therapy with an SGLT2 inhibitor plus a GLP-1 agonist provide additive cardiorenal benefits in CKD patients?
- Would tirzepatide change the GLP-1 RA class rankings if included as a separate analysis?
- At what CKD stage should SGLT2 inhibitors be preferentially started over GLP-1 agonists?
Common questions
Which diabetes drug is best for protecting the kidneys?
Should diabetic kidney disease patients take both types of drugs?
Read the original research
Comparative analysis on renal and cardiovascular outcomes of antidiabetic treatment in chronic kidney disease patients-A systematic review and network meta-analysis.
Diabetes, obesity & metabolism, 27(11), 6254-6263
Citation
Bramlage, Peter; Vijayan, Anjaly; Varghese, Treesa P; Melepurakkal Sadanandan, Deepthy; Lanzinger, Stefanie; Rodriguez, Carmen Ferrero. (2025). Comparative analysis on renal and cardiovascular outcomes of antidiabetic treatment in chronic kidney disease patients-A systematic review and network meta-analysis.. Diabetes, obesity & metabolism, 27(11), 6254-6263. https://doi.org/10.1111/dom.70010