974-P: Network Meta-analysis of Once Weekly Glucagon-Like Peptide-1 Receptor Agonists: A Focus on Cardiovascular Safety and Mortality

Objective: To indirectly compare once weekly exenatide, semaglutide, albiglutide and dulaglutide regarding cardiovascular (CV) safety and mortality using network meta-analysis (NMA). Methods: PubMed was searched to identify glucagon like peptide-1 receptor agonists (GLP-1RA) outcome trials (CVOTs) to date. The outcomes of interest were CV death, myocardial infarction (IM), nonfatal MI, stroke, nonfatal stroke, death from any cause, and hospitalizations for heart failure (HF). An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. Data were extracted by two independent reviewers and risk of bias was assessed in the same manner. Results: The NMA results showed no significant differences among the four GLP-1RAs regarding most of the outcomes. However, albiglutide when compared to exenatide was associated with lower risk of MI (HR 0.76, 95% Cl: 0.60-0.96)] and nonfatal MI (HR 0.76, 95% Cl: 0.60-0.97). The ranking probability showed that semaglutide had the highest probability to be ranked first in reducing MI (55%), nonfatal MI (55%), stroke (87%), and nonfatal stroke events (87%). For CV death and death from any cause, exenatide had the highest probability to be ranked first at 30% and 45% respectively. Lastly, for hospitalizations for HF, albiglutide was ranked first with a probability of 55% followed by placebo. Conclusion: This NMA did not show significant differences among the treatments. However, based on the ranking results, semaglutide seems to be the preferred agent over the other once weekly GLP-1RAs in patients with diabetes and CV risk.