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

Holman, Rury R. and Bethel, M. Angely and Mentz, Robert J. and Thompson, Vivian P. and Lokhnygina, Yuliya and Buse, John B. and Chan, Juliana C. and Choi, Jasmine and Gustavson, Stephanie M. and Iqbal, Nayyar and Maggioni, Aldo P. and Marso, Steven P. and Öhman, Peter and Pagidipati, Neha J. and Poulter, Neil and Ramachandran, Ambady and Zinman, Bernard and Hernandez, Adrian F. and Ukraine, : and Koval, Olena and Larin, Oleksandr and Levchenko, Olena and Martynyuk, Lilya and Maslyanko, Vitaliy and Rudyk, Iurii and Suprun, Yevgen and Tseluyko, Vira and Botsyurko, Volodymyr and Vatutin, Mykola and Fushtey, Ivan and Grishyna, Olena and Kuskalo, Petro and Panina, Svitlana and Pererva, Larys and Prysupa, Liudmyla and Teliatnikova, Zinaida and Sokolova, Lyubov and Vlasenko, Maryna and Berenfus, Vadym and Parkhomenko, Olexander and Gyrina, Olga and Kopytsya, Mykola and Vizir, Vadym and Vayda, Myroslava (2017) Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. The New England Journal of Medicine = N Engl J Med, 377. pp. 1228-1239. ISSN 0028-4793 (print); 1533-4406 (online)

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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.)

Item Type:	Article
Additional Information:	DOI: 10.1056/NEJMoa1612917 https://www.nejm.org/doi/full/10.1056/nejmoa1612917
Subjects:	Internal Medicine
Divisions:	Departments > Department of Internal Medicine 3 (formerly - hospital therapy 2)
Depositing User:	Елена Шрамко
Date Deposited:	30 Nov 2020 09:50
Last Modified:	30 Nov 2020 09:52
URI:	http://repo.dma.dp.ua/id/eprint/6017

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