Fig. 1

A timeline of published diabetes CVOTs. The comparator in all trials was placebo, unless otherwise stated. Primary endpoints for each trial are listed. 3/4P-MACE, 3/4-point major adverse CV event; CV, cardiovascular; DPP-4, dipeptidyl peptidase-4; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HHF, hospitalisation for heart failure; SGLT2, sodium–glucose transporter 2. Source: clinicaltrials.gov. *3P-MACE is a composite of CV death, nonfatal myocardial infarction and nonfatal stroke. 4P-MACE is an expanded composite of 3P-MACE plus either hospitalisation for unstable angina (ELIXA, TECOS and FREEDOM-CVO) or death from undetermined causes (AMPLITUDE-O). ^†TECOS and FREEDOM-CVO included 3P-MACE as a secondary outcome. ^‡CAROLINA was conducted in addition to regulatory requirements, as an active-controlled CVOT complementary to the core placebo-controlled CVOT CARMELINA. ^§Albiglutide is no longer a licensed treatment. ^‖Efpeglenatide is not a currently licensed treatment. ^¶FREEDOM-CVO (exenatide subcutaneous implant; not a currently licensed treatment) was completed in 2016, but the primary outcome (4P-MACE) was reported in 2022