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

R. R. Holman, M. A. Bethel, R. J. Mentz, V. P. Thompson, Y. Lokhnygina, J. B. Buse, J. C. Chan, J. Choi, S. M. Gustavson, N. Iqbal, A. P. Maggioni, S. P. Marso, P. Ohman, N. J. Pagidipati, N. Poulter, A. Ramachandran, B. Zinman, A. F. Hernandez, EXSCEL Study Group

Research output: Contribution to journalArticle

Abstract

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
Original languageEnglish
Pages (from-to)1228-1239
Number of pages12
JournalNew England Journal of Medicine
Volume377
Issue number13
DOIs
Publication statusPublished - Sep 28 2017

Keywords

  • Aged
  • Cardiovascular Diseases/complications/epidemiology/mortality/prevention & control
  • Diabetes Mellitus, Type 2/blood/complications/drug therapy
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypoglycemic Agents/administration & dosage/adverse effects
  • Incidence
  • Injections, Subcutaneous
  • Kaplan-Meier Estimate
  • Least-Squares Analysis
  • Male
  • Middle Aged
  • Peptides/administration & dosage/adverse effects
  • Venoms/administration & dosage/adverse effects

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    Holman, R. R., Bethel, M. A., Mentz, R. J., Thompson, V. P., Lokhnygina, Y., Buse, J. B., Chan, J. C., Choi, J., Gustavson, S. M., Iqbal, N., Maggioni, A. P., Marso, S. P., Ohman, P., Pagidipati, N. J., Poulter, N., Ramachandran, A., Zinman, B., Hernandez, A. F., & Group, EXSCEL. S. (2017). Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. New England Journal of Medicine, 377(13), 1228-1239. https://doi.org/10.1056/NEJMoa1612917 [doi]