TABLE 2.

Studies Evaluating MACE with Once-Weekly GLP-1 RAs

Exenatide QW: EXSCEL trial61
Study population	Adults with T2DM, with or without previous CV disease; patients could receive ≤ 3 OADs or insulin + ≤ 2 OADs (73.1% with prior CV disease)
Number/observation period	Exenatide QW, n = 7,356; placebo, n = 7,396 Median observation period = 3.2 years
CV-related endpoints	Primary: Composite outcome: first occurrence of death from CV causes, nonfatal MI, or nonfatal stroke Secondary: Death from any cause, death from CV causes, and the first occurrence of nonfatal or fatal MI, nonfatal or fatal stroke, hospitalization for acute coronary syndrome, and hospitalization for heart failure in time-to-event analyses
Topline findings	Primary: 11.4% in the exenatide group (3.7 events per 100 person-years) vs. 12.2% in the placebo group (4.0 events per 100 person-years; HR = 0.91; 95% CI = 0.83-1.00) Secondary: The rates of the first fatal or nonfatal MI, fatal or nonfatal stroke, and other secondary outcomes were not significantly different between the 2 groups
Conclusions	The incidence of MACE was not significantly different between exenatide QW and placebo treatment
Dulaglutide: REWIND trial (ongoing)62
Study population	Newly diagnosed T2DM patients with A1c ≤ 9.5% treated with ≤ 2 classes of OADs, with or without basal insulin Additional eligibility requirements: 50-54 years of age: previous CV disease; 50-59 years of age: either previous CV disease or evidence of other vascular or renal disease; aged ≥ 60 years: previous CV disease, other vascular or renal disease, or ≥ 2 other CV risk factors
Number/observation period	9,901 participants recruited Mean duration of follow-up: 6.5 years
CV-related endpoints	Primary: First occurrence of the composite of cardiovascular death or nonfatal MI or nonfatal stroke Secondary: Each component of the primary composite CV outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality
Topline findings	TBD (expected completion July 2018)
Conclusions	TBD (expected completion July 2018)
Semaglutide: SUSTAIN-6 study50
Study population	Patients ≥ 50 years of age with T2DM and A1c ≥ 7% treated with ≤ 2 OADs ± basal or premixed insulin Patients were at high CV risk
Number/observation period	Semaglutide, n = 1,648; placebo, n = 1,649 Median observation period = 2.1 years
CV-related endpoints	Primary: Composite outcome: first occurrence of CV death, nonfatal MI, or nonfatal stroke Secondary: First occurrence of an expanded composite CV outcome (death from CV causes, nonfatal MI, nonfatal stroke, revascularization [coronary or peripheral], and hospitalization for unstable angina or heart failure), an additional composite outcome (death from all causes, nonfatal MI, or nonfatal stroke), or the individual components of the composite outcome
Topline findings	Primary: Semaglutide-treated patients had a significant 26% lower risk of the primary composite outcome; 6.6% in the semaglutide group vs. 8.9% in the placebo group (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001 for noninferiority) Secondary: Nonfatal MI occurred in 2.9% of patients receiving semaglutide vs. 3.9% of those receiving placebo (HR = 0.74; 95% CI = 0.51-1.08; P = 0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (HR = 0.61; 95% CI = 0.38-0.99; P = 0.04); expanded composite CV outcome: 12.1% with semaglutide vs. 16.0% with placebo (HR = 0.74; 95% CI = 0.62-0.89); the following were not significantly different between groups (P ≥ 0.05): death from any cause, death from CV cause, nonfatal MI, hospitalization for unstable angina, hospitalization for heart failure
Conclusions	The rate of MACE was significantly lower in patients receiving semaglutide compared with those receiving placebo and confirmed the noninferiority of semaglutide

A1c = glycated hemoglobin; CI = confidence interval; CV = cardiovascular; GLP-1 RA = glucagon-like peptide-1 receptor agonist; HR = hazard ratio; MACE = major adverse cardiovascular event; MI = myocardial infarction; OAD = oral antidiabetic drug; QW = once weekly; T2DM = type 2 diabetes mellitus; TBD = to be determined.