Background: This systematic review and network meta-analysis compared the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2Is) , glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP4Is) on cardiovascular (CV) and renal outcomes in patients with diabetic kidney disease (DKD) (INPLASY2021120070) .

Methods: The MEDLINE database was searched systematically to identify articles that reported CV and renal outcomes from Phase III or IV randomised, placebo-controlled trials after intervention with SGLT2Is, GLP-1 RAs or DPP4Is in patients with DKD. HRs and 95% CIs were calculated using a network meta-analysis.

Results: 16 trials representing a total of 46,292 patients were analysed. SGLT2Is significantly reduced the risks of kidney-specific composite outcome by 26% (HR=0.74, 95% CI 0.62-0.88) and 36% (HR=0.64, 95% CI 0.52-0.79) ; and the risks of hospitalisation for heart failure (HHF) by 28% (HR=0.72, 95% CI 0.56-0.92) and 41% (HR=0.59, 95% CI 0.49-0.71) , compared to GLP-1 RAs and DPP4Is respectively. SGLT2Is also reduced the risk of major adverse cardiovascular events (MACE) by 18% (HR=0.82, 95% CI 0.69-0.96) compared to DPP4Is. The risk of MACE was comparable between SGLT2Is and GLP-1 RAs (HR=0.95, 95% CI 0.82-1.10) . The risk of CV death was not significantly different between the three treatments.

Conclusions: This meta-analysis integrated data from recent high-quality CV and renal outcome trials, providing high statistical power. SGLT2Is significantly lowered risks of kidney-specific outcome, MACE and HHF compared to DPP4Is and placebo, and reduced risks of kidney-specific outcome and HHF compared to GLP-1 RAs. GLP-1 RAs also showed CV and renal outcome benefits compared to placebo, but not compared to SGLT2Is or DPP4Is for most outcomes. DPP4Is did not improve either CV or renal outcomes compared to placebo.


H.Cao: None. T.Liu: None. L.Wang: None. Q.Ji: None.

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