Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.
Date
2017-09
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
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<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 .).Type
Department
Description
Provenance
Subjects
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Holman, Rury R, M Angelyn Bethel, Robert J Mentz, Vivian P Thompson, Yuliya Lokhnygina, John B Buse, Juliana C Chan, Jasmine Choi, et al. (2017). Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. The New England journal of medicine, 377(13). pp. 1228–1239. 10.1056/nejmoa1612917 Retrieved from https://hdl.handle.net/10161/30420.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Yuliya Vladimirovna Lokhnygina
Statistical methods in clinical trials, survival analysis, adaptive designs, adaptive treatment strategies, causal inference in observational studies, semiparametric inference
Neha Pagidipati
Neha J. Pagidipati, MD, MPH, is an Assistant Professor of Medicine and cardiovascular disease prevention specialist. Since 2011, she has conducted research on cardiometabolic disease prevention, lifestyle modification and weight management. She is currently an NIH K12 scholar in Implementation and Dissemination Science.
Dr. Pagidipati is building the Duke Cardiometabolic Disease Prevention Program, which focuses on behavior change and risk factor management in patients with high risk of cardiovascular and metabolic diseases such as diabetes and obesity. The program’s multi-disciplinary team of cardiologists, endocrinologists, nephrologists, and hepatologists will work together to provide coordinated, team-based care to the most high-risk and complex patients in the health system.
Dr. Pagidipati’s research grants include the COORDINATE-Diabetes Trial, to improve the quality of care for patients with diabetes and cardiovascular disease across the U.S., and QuBBD: Deep Poisson Methods for Biomedical Time-to-Event and Longitudinal Data. She served as a study clinician on the large, longitudinal EXSCEL (Exenatide Study of Cardiovascular Event Lowering) trial. She is currently conducting a nation-wide study of obesity management using real-world data sources, and is a site investigator for the Baseline Health Study in collaboration with Verily Life Sciences. In addition, she is leading a large study within the Duke Health System to study heterogeneity within cardiovascular disease risk and response to weight loss interventions among individuals with obesity.
Dr. Pagidipati graduated from Harvard College and Harvard Medical School. She completed her internal medicine residency at Brigham and Women’s Hospital. During a two-year research fellowship in Global Women’s Health at the Brigham, she obtained an MPH from the Harvard School of Public Health and studied cardiovascular disease prevention in women in India. Dr. Pagidipati completed a four-year cardiology fellowship at the Duke University School of Medicine and served as Chief Research Fellow at the Duke Clinical Research Institute. In 2017, she became a faculty member of the Duke University School of Medicine School.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.