Effects of once‐weekly glucagon‐like peptide‐1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin‐angiotensin system.

Aim: To investigate the potential mechanism of once‐weekly glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) in the treatment of type 2 diabetes mellitus (T2DM) complicated with coronary artery disease (CAD). Methods: We searched both Chinese and English databases for randomized controlled trials related to once‐weekly GLP‐1 RA for T2DM complicated with CAD to verify the safety and efficacy of GLP‐1 RA. The underlying mechanism was analysed by network pharmacology. Results: In total, 13 studies with 35 563 participants were included in the analysis. The pooled analysis found that dulaglutide, exenatide and semaglutide outperformed placebo in cardiovascular outcomes in patients with T2DM, with a significant reduction in the incidence of non‐fatal stroke (p <.00). Levels of cardiovascular risk factors were significantly reduced in the once‐weekly GLP‐1 RA group compared with the conventional treatment group (glycated haemoglobin: p <.00; fasting blood glucose: p <.00; weight: p <.00; systolic blood pressure: p <.00; total cholesterol: p <.00; low‐density lipoprotein cholesterol: p <.00). Network pharmacology results were enriched to the renin‐angiotensin system, and matrix metalloproteinase 2 and renin (REN) may be the key targets. In addition, four key targets of dulaglutide, five key targets of exenatide and two key targets of semaglutide were enriched. Conclusions: Our study suggests that once‐weekly GLP‐1 RA may have a potential protective effect on cardiovascular events in patients with T2DM combined with CAD, possibly through the renin‐angiotensin system. However, further research is needed to confirm these findings and determine cause and effect. [ABSTRACT FROM AUTHOR]