Comparative efficacy of sodium‐glucose co‐transporter‐2 inhibitors, glucagon‐like peptide‐1 receptor agonists and non‐steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta‐analysis

Abstract Aim To compare the relative efficacy of sodium‐glucose co‐transporter 2 inhibitors (SGLT‐2is), glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and non‐steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Materials and Methods We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow‐up of at least 24 weeks and compared SGLT‐2is, GLP‐1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all‐cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs). Results Twenty‐nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT‐2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP‐1RAs (RR, 0.77; 95% CI, 0.64‐0.91; P = .003) and nsMRAs (RR, 0.78; 95% CI, 0.68‐0.90; P = .001). Compared with GLP‐1RAs and nsMRAs, SGLT‐2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55‐0.88; P = .002) and 22% (RR, 0.78; 95% CI, 0.63‐0.95; P = .016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP‐1RAs and nsMRAs in lowering all outcomes. Conclusions SGLT‐2is were associated with better cardiorenal protection than GLP‐1RAs and nsMRAs in patients with CKD and T2D.