Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with kidney outcomes in patients with type 2 diabetes: A systematic review and network meta-analysis

Background: This study aimed to compare the efficacies of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors on kidney outcomes in patients with type 2 diabetes using network meta-analysis. Methods: PubMed, EMBASE, and CENTRAL were searched for studies published up to September 28, 2020. Randomized clinical trials enrolling participants with type 2 diabetes were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other, or placebo or no treatment. A network meta-analysis using a Bayesian approach was performed. The primary outcome was composite renal events, and the secondary outcome was acute kidney injury (AKI) events. All research was conducted according to a protocol registered in the PROSPERO database (CRD42020208090). Results: In total, we retrieved 17 445 studies, of which 98 articles enrolling 186 335 participants were included for the network meta-analysis. For our primary outcome, the network meta-analysis revealed no significant difference between drug classes regardless of baseline factors. However, GLP-1 receptor agonists were most likely ranked best among the three drugs in reducing composite renal events (80%, moderate-quality evidence). Compared with the control groups (OR 0.74, 95% CI 0.62 to 0.87, low-quality evidence), GLP-1 receptor agonists (OR 0.76, 95% CI 0.59 to 0.96, moderate-quality evidence) and with DPP-4 inhibitors (OR 0.67, 95% CI 0.50 to 0.86, low-quality evidence), SGLT-2 inhibitors were associated with a lower risk of AKI events. Conclusions: In this network meta-analysis, although none of the three new antidiabetic drug classes reduced the composite renal events in participants with type 2 diabetes, GLP-1 receptor agonists may be more effective. The use of SGLT-2 inhibitors was associated with a lower AKI event risk than DPP-4 inhibitors, GLP-1 agonists, placebo, or no treatment.