Effects of Antidiabetic Drugs on Endothelial Function in Patients With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis

Abstract

Background: The changes of endothelial function in type 2 diabetes mellitus (T2DM) patients are closely associated with the development of cardiovascular disease (CVD). However, it is still unclear whether commonly used antidiabetic drugs can improve endothelial function. Flow-mediated dilation (FMD) is a noninvasive tool for evaluating endothelial function, which typically examines changes in the brachial artery diameter in response to ischemia using ultrasound. We performed a network meta-analysis (NMA) to explore the associations between changes in endothelial function and antidiabetic drugs by evaluating FMD in T2DM patients.

Methods: We systematically searched several electronic databases for randomized controlled trials (RCTs) published from inception until January 25, 2022 with no language restriction. The primary outcome was FMD change in all studies, and we performed subgroup analysis in T2DM patients without CVD. NMA was performed to calculate the mean differences (MDs) with 95% confidence intervals (CIs).

Results: From the 1,987 candidate articles identified in the initial search, 30 RCTs were eventually included in the analysis. In all studies, glucagon-like peptide-1 receptor (GLP-1R) agonists [MD = 3.70 (1.39-5.97)], TZD [MD = 1.96 (0.006-3.89)] produced improvement of FMD change compared to lifestyle intervention. GLP-1R agonists [MD = 3.33 (1.36-5.34) and MD = 3.30 (1.21-5.43)] showed significantly greater improvements in FMD change in pairwise comparisons with sulfonylureas and placebo. SGLT-2i also showed efficacy compared to sulfonylureas (MD = 1.89, 95% CI, 0.10, 3.75). In studies of T2DM patients without CVD, GLP-1R agonists [MD = 3.53 (1.24-5.76)], and TZD [MD = 2.30 (0.27-3.24)] produced improvements in FMD change compared to lifestyle treatment. GLP-1R agonists [MD = 3.25 (1.13-5.40), and MD = 3.85 (1.68-6.13)] showed significantly greater improvements in pairwise comparisons with sulfonylureas, and placebo.

Conclusion: In T2DM patients, both GLP-1R agonists, SGLT-2i and TZD have favorable effects to improve endothelial function in T2DM patients. In T2DM patients without CVD, GLP-1R agonists had a greater effect to improve endothelial function than sulfonylureas. These suggested that GLP-1R agonists are associated with significantly improved endothelial function in T2DM patients.

Keywords: antidiabetic drugs; diabetes; endothelial function; flow-mediated dilation; meta-analysis; type 2.

Figure 1

Study selection flow chart.

Figure 2

Network Plot for all studies. GLP-1 RA, glucagon-like peptide-1 receptor agonist. SGLT-2i, sodium-glucose co-transporter 2 inhibitor. DPP-4i, dipeptidyl peptidase-4 inhibitor. TZD, Thiazolidinedione. Lifestyle,exercise and/or diet.