Individual dipeptidyl peptidase-4 inhibitors and acute kidney injury in patients with type 2 diabetes: A systematic review and network meta-analysis.

This network meta-analysis of randomized controlled trials aimed to determine whether any individual dipeptidyl peptidase-4 (DPP-4) inhibitors increase the risk of acute kidney injury (AKI). The Medical Literature Analysis and Retrieval System Online via PubMed, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were systematically searched to identify relevant studies. The primary outcome was AKI. A frequentist network meta-analysis was performed using a random-effects model to account for heterogeneity. Twenty-nine studies involving 56 117 participants were included. There were 918 cases of AKI (1.63%). The risk of bias was generally considered to be low. The only DPP-4 inhibitor that significantly increased the frequency of AKI when compared with placebo was sitagliptin (risk ratio 1.65, 95% confidence interval 1.22-2.23). However, because one study showed significant outliers in the funnel plot, in a highly heterogeneous population composed solely of patients undergoing surgery for coronary artery bypass graft, we conducted a post-hoc sensitivity analysis to exclude this study. The results showed no statistically significant difference in the risk of AKI between sitagliptin and placebo. Individual DPP-4 inhibitors do not appear to increase the risk of AKI. However, sitagliptin may be associated with AKI in patients with underlying severe cardiovascular disease.

Urate-Lowering Drugs and Muscle Injury: A Systematic Review and Network Meta-Analysis.

Several urate-lowering drugs have been linked to muscle injury. This study investigated the association of oral urate-lowering drugs with the risk of muscle injury by performing a network meta-analysis of randomized and non-randomized controlled trials. A systematic search of MEDLINE, via PubMed, the ClinicalTrials.gov website, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant studies with a primary outcome of "all muscle injuries." A random-effects model was used to perform a frequentist network meta-analysis to estimate whether there was significant heterogeneity among the studies. In total, 32 studies including 28,327 participants with 2694 (9.5%) "all muscle injuries" were assessed, and the overall risk of bias was judged to be low to moderate. No statistically significant differences were found between placebo and 6 urate-lowering therapies: allopurinol (risk ratio, RR, 1.05; 95% confidence interval, 95%CI, 0.63-1.73), febuxostat (RR 1.10, 95%CI 0.71-1.70), lesinurad (RR 7.00, 95%CI 0.31-160.36), lesinurad concomitant with allopurinol (RR 0.85, 95%CI 0.34-2.11), lesinurad concomitant with febuxostat (RR 1.97, 95%CI 0.55-7.03), and topiroxostat (RR 0.99, 95%CI 0.37-2.65). The findings suggest that there is little need to consider the risk of muscle injury when using urate-lowering drugs in the clinical setting.