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.
Competing Interests: Declaration of competing interest MMYL's employer, the University of Glasgow, has received grant support from Boehringer Ingelheim. SLK reports speaker fees from AstraZeneca, outside the submitted work. HCG holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, MSD, Novo Nordisk, and Sanofi; honoraria for speaking from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, DKSH, and Zuellig; and consulting fees from Abbott, Covance, Eli Lilly, Novo Nordisk, Sanofi, Pfizer, Kowa, and Hanmi. JJVM acknowledges payments to his employer, the University of Glasgow, for his work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Theracos; personal lecture fees from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, theheart.org, ProAdWise Communications, Radcliffe Cardiology, Servier, and the Corpus. NS has consulted for or received lecture fees from Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi; and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics through his institution, the University of Glasgow.
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