TY - JOUR
T1 - Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes
AU - Holman, Rury R.
AU - Bethel, M. Angelyn
AU - Mentz, Robert
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 - for the EXSCEL Study Group
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 - Pozzi, Emanuela
AU - Oulhaj, Abderrahim
AU - Coleman, Ruth
AU - Rouleau, Jean Lucien
AU - Pocock, Stuart J.
AU - Gorelick, Fred
AU - McMurray, John
AU - Riddle, Matt
AU - Gagel, Robert
AU - Collier, Tim
AU - Markovic, Tania
AU - Kong, Alice Pik Shan
AU - Hian, Sim Kui
AU - Scott, Russell
AU - Panelo, Araceli
AU - Yoon, Kun Ho
AU - Sheu, Wayne
AU - Sritara, Piyamitr
AU - Linong, Ji
AU - Pan, Chanyu
AU - Yong, Huo
AU - Schernthaner, Guntram
AU - Mathieu, Chantal
AU - Tankova, Tsvetalina
AU - Widimsky, Petr
AU - Hanefeld, Markolf
AU - Keltai, Matyas
AU - Wainstein, Julio
AU - Del Prato, Stefano
AU - Pirags, Valdis
AU - Jakuboniene, Neli
AU - Kooy, Adriaan
AU - Dziemidok, Piotr
AU - Veresiu, Ioan Andrei
AU - Dreval, Alexander V.
AU - Murin, Jan
AU - Torello, Albert Le Cube
AU - Sattar, Naveed
AU - Parkhomenko, Olexander
AU - Omar, Mohamed
AU - Diaz, Rafael
AU - Lopes, Renato
AU - Lanas, Fernando
AU - Triana, Miguel Urina
AU - Leiva-Pons, Jose Luis
AU - Aguliera, David
AU - Bergenstal, Richard
AU - Goodman, Shaun
AU - Yale, Jean Francois
AU - Caterson, Ian
AU - Weng, Jianping
AU - Hu, Dayi
AU - Junbo, Ge
AU - Zannad, Faiez
AU - Anoop, Misra
AU - Ambrish, Mithal
AU - Gallegos, John Adaly
AU - Green, Jennifer B.
AU - Akerblom, Axel
AU - Alexander, Karen
AU - Al-Khatib, Sana
AU - Armaganijan, Luciana
AU - Barros, Pedro
AU - Batit, Maria
AU - Bernacki, Gwen
AU - Bernandez, Sabrina
AU - Bloomfield, Gerald
AU - Clausen, Emily
AU - De Souza Brito, Flavio
AU - DeVore, Adam
AU - Dombrowski, Keith
AU - Eapen, Zubin
AU - Gellad, Ziad
AU - George, Daniel
AU - Guimaraes, Patricia
AU - Halim, Sharif
AU - Harrison, Rob
AU - Hawes, Jodi
AU - Hess, Connie
AU - Hyland, Kristen
AU - Jackson, Larry
AU - Jones, Schuyler
AU - Jordan, Dedrick
AU - Katz, Marcelo
AU - Kong, David
AU - Koshizaka, Masaya
AU - Lakey, Wanda
AU - LeBlanc, Thomas
AU - Leonardi, Sergio
AU - Lopes, Renato
AU - Luo, Nancy
AU - Mahaffey, Ken
AU - Mandawat, Aditya
AU - Mehta, Rajendra
AU - Melloni, Chiara
AU - Mentz, Robert
AU - Morse, Michael
AU - Pagidpati, Neha
AU - Patel, Chetan
AU - Patel, Keyur
AU - Pokorney, Sean
AU - Posvic, Tom
AU - Rao, Meena
AU - Roe, Matthew
AU - Shah, Bimal
AU - Tillmann, Hans
AU - Truffa, Adriano
AU - Wong, Yee Weng
AU - Zazula, Ana
AU - Zeitler, Emily
AU - Sicer, Maximiliano
AU - Ulla, Maria Rosa
AU - Maffei, Laura
AU - Klyver, Maria Isabel
AU - Calella, Pedro
AU - Alvarisqueta, Andrés
AU - De La Fuente, Ricardo Leon
AU - Aizenberg, Diego
AU - Roque, Fernando
AU - Cruciani, Adrian
AU - Frechtel, Gustavo
AU - Gelersztein, Elizabeth
AU - Villarino, Adriana
AU - Mallagray, Marcelo
AU - Nardone, Lucrecia
AU - Zaidman, Cesar
AU - Novaretto, Leonardo
AU - Bartolacci, Ines
AU - De Salvo, Maria
AU - Delcourt, Candice
AU - Crimmins, Denis
AU - Jackson, Richard
AU - O'Neal, David
AU - Colman, Peter
AU - Jeffries, William
AU - Mah, Peak Mann
AU - Wittert, Gary
AU - Markovic, Tania
AU - Proietto, Joseph
AU - Amerena, John
AU - Marks, Sharon
AU - Tan, Ren
AU - Colquhoun, David
AU - Pieber, Thomas
AU - Drexel, Heinz
AU - Prager, Rudolf
AU - Schnack, Christoph
AU - Hoppichler, Fredrich
AU - Fasching, Peter
AU - Francesconi, Claudia
AU - Luger, Anton
AU - Schoenherr, Hans Robert
AU - Ebenbichler, Christoph
AU - Paulweber, Bernhard
AU - Shernthaner, Guntram
AU - Verhaegen, Ann
AU - Vanuytsel, Johan
AU - Mathieu, Chantal
AU - Thissen, Jean Paul
AU - Barros E Silva, Pedro
AU - Lopes, Renato
AU - Gonzaga, Carolina
AU - Borges, Joao
AU - Hissa, Miguel
AU - Rea, Rosangela
AU - Rossi, Paulo
AU - Chacra, Antonio
AU - Eliaschewitz, Freddy
AU - Garbelini, Benito
AU - Felicio, Joao
AU - Rassi, Nelson
AU - Rossi, Fabio
AU - Dos Santos, Mayler Nunes
AU - Bandeira E Farias, Francisco
AU - Lisboa, Hugo
AU - Costa E Forti, Adriana
AU - Saraiva, José Kerr
AU - Tankova, Tsvetalina
AU - Kovacheva, Snejina
AU - Levterov, Georgi
AU - Sheinkova, Galina
AU - Ilieva, Elena
AU - Lyubenova, Lyudmila
AU - Damyanova, Velichka
AU - Gushterova, Valentina
AU - Mincheva, Lilyana
AU - Illiev, Dimitar
AU - Ivanov, Valentin
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 -