Exenatide once-weekly is an extended release formulation of exenatide, a glucagon-like peptide–1 receptor agonist, which canimprove glycemic control, body weight, blood pressure, and lipid levels in patients with type 2 diabetes mellitus (T2DM). TheEXenatide Study of Cardiovascular Event Lowering (EXSCEL) will compare the impact of adding exenatide once-weekly to usualcare with usual care alone on major cardiovascular outcomes.EXSCEL is an academically led, phase III/IV, double-blind, pragmatic placebo-controlled, global trial conducted in 35countries aiming to enrol 14,000 patients with T2DM and a broad range of cardiovascular risk over approximately 5 years.Participants will be randomized (1:1) to receive exenatide once-weekly 2 mg or matching placebo by subcutaneous injections.The trial will continue until 1,360 confirmedprimary composite cardiovascular end points, defined as cardiovascular death,nonfatal myocardial infarction, or nonfatal stroke, have occurred.The primary efficacy hypothesis is that exenatide once-weekly is superior to usual care with respect to the primary compositecardiovascularend point. EXSCEL is powered todetect a 15% relativerisk reduction inthe exenatide once-weekly group, with 85%power anda 2-sided 5%alpha.Theprimary safetyhypothesis is thatexenatideonce-weeklyis noninferior tousualcarewithrespectto the primary cardiovascular composite end point. Noninferiority will be concluded if the upper limit of the CI isb1.30.EXSCEL will assess whether exenatide once-weekly can reduce cardiovascular events in patients with T2DM with a broadrange of cardiovascular risk. It will also provide long-term safety information on exenatide once-weekly in people with T2D
