TY - JOUR

T1 - Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

AU - EXSCEL Study Group

AU - Holman, Rury R

AU - Bethel, M Angelyn

AU - Mentz, Robert J

AU - Thompson, Vivian P

AU - Lokhnygina, Yuliya

AU - Buse, John B

AU - Chan, Juliana C

AU - Choi, Jasmine

AU - Gustavson, Stephanie M

AU - Iqbal, Nayyar

AU - Maggioni, Aldo P

AU - Marso, Steven P

AU - Öhman, Peter

AU - Pagidipati, Neha J

AU - Poulter, Neil

AU - Ramachandran, Ambady

AU - Zinman, Bernard

AU - Hernandez, Adrian F

AU - Обрезан, Андрей Григорьевич

PY - 2017/9/28

Y1 - 2017/9/28

N2 - BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups.CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).

AB - BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups.CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).

KW - Aged

KW - Cardiovascular Diseases/complications

KW - Diabetes Mellitus, Type 2/blood

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Exenatide

KW - Female

KW - Humans

KW - Hypoglycemic Agents/administration & dosage

KW - Incidence

KW - Injections, Subcutaneous

KW - Kaplan-Meier Estimate

KW - Least-Squares Analysis

KW - Male

KW - Middle Aged

KW - Peptides/administration & dosage

KW - Venoms/administration & dosage

U2 - 10.1056/NEJMoa1612917

DO - 10.1056/NEJMoa1612917

M3 - Article

C2 - 28910237

VL - 377

SP - 1228

EP - 1239

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 13

ER -