Cardiovascular and mortality outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a meta-analysis with the FREEDOM cardiovascular outcomes trial

Background and aims: FREEDOM, a cardiovascular outcome trial with a GLP-1 receptor agonist, testing a continuous subcutaneous infusion of exenatide (ITCA 650), recently reported its findings. Methods: We meta-analysed its results with eight prior GLP-1 receptor agonists trials. Results: GLP-1 receptor agonists reduced MACE by 13% (HR 0.87 [95% CI 0.81–0.94]; p = 0.00065) and all-cause mortality by 11% (HR 0.89 [0.83–0.95]; p = 0.00084). However, FREEDOM results appear dissimilar to prior GLP-1 receptor agonist trials. Conclusion: FREEDOM results should not influence current considerations about the benefits or harms of approved formulations of GLP-1 receptor agonists. There is also an ongoing debate about the safety of ITCA 650