TY - JOUR
T1 - Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes
AU - for the 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 - Califf, Robert M.
AU - Patel, Rishi
AU - George, Jyothis
AU - Sourij, Harald
AU - Wong, Yee Weng
AU - Hannan, Karen
AU - Gottlieb, Pat
AU - Meadows, Yolanda
AU - Elkins, Mary
AU - Perkins, Lynn
AU - Wilson, Matt
AU - Stone, Allegra
AU - Tisch, Andrea
AU - Kennedy, Irene
AU - Heal, Paul
AU - Masterson, Michelle
AU - Darbyshire, Julie
AU - Mumtaz, Lorraine
AU - Athwal, Rajbir
AU - Ferch, Andrea
AU - Batra, Priyanka
AU - Durborow, Lynne
AU - Vincent, Jennifer
AU - Woodall, Andrew
AU - Flanagan, Terry
AU - Gustavson, Stephanie
AU - Choi, Jasmine
AU - Katona, Brian
AU - Reicher, Barry
AU - Thompson, Vivian
AU - Lokhnygina, Yuliya
AU - Pirags, Valdis
N1 - Publisher Copyright:
Copyright © 2017 Massachusetts Medical Society.
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.
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.
UR - https://www.scopus.com/pages/publications/85030448557
U2 - 10.1056/NEJMoa1612917
DO - 10.1056/NEJMoa1612917
M3 - Article
C2 - 28910237
AN - SCOPUS:85030448557
SN - 0028-4793
VL - 377
SP - 1228
EP - 1239
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 13
ER -
SDG 3 Good Health and Well-being