Comparative effects of glucose-lowering agents on endothelial function and arterial stiffness in patients with type 2 diabetes: A network meta-analysis

Background and aims: Despite accumulating evidence on the potential of glucose -lowering agents (GLAs) to prevent cardiovascular events, the comparative effects of GLAs on vascular function remain unclear. This study utilized validated indicators such as flow -mediated dilation (FMD; positive value favors) and pulse wave velocity (PWV; negative value favors) to uncover the comparative effects of GLAs on vascular function. Methods: Randomized controlled trials (RCTs) comparing the effects of GLAs on FMD or PWV with placebo or other GLAs in patients with type 2 diabetes (T2DM) were searched through PubMed and Embase. The frequentist method of network meta -analysis (NMA) was conducted using a random effects model, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Results: The NMA included 38 RCTs with 2,065 patients. Glucagon-like peptide -1 receptor agonists (GLP-1RAs) and sodium glucose cotransporter-2 inhibitors (SGLT-2Is) had significantly more positive effects on FMD improvement and PWV reduction than placebo. Thiazolidinedione (TZD) treatment resulted in significantly improved FMD compared to other GLAs as well as placebo (SMD: 1.14; 95% CI: 0.84 to 1.43). Both pioglitazone and rosiglitazone were discovered to have considerably more favorable effects on improving FMD and reducing PWV compared to placebo and other GLAs, as a result of the analysis incorporating each drug in the TZD class. The sensitivity analysis results corroborated the main findings. Conclusions: This NMA showed more favorable effects of GLP-1RAs and SGLT-2Is than placebo in improving both arterial stiffness and endothelial function in patients with T2DM. In addition, TZDs showed superior effects in improving endothelial function as compared with the other GLAs and placebo.