Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

Rury R. Holman, M. Angelyn Bethel, Robert J. Mentz, Vivian P. Thompson, Yuliya Lokhnygina, John B. Buse, Juliana C. Chan, Jasmine Choi, Stephanie M. Gustavson, Nayyar Iqbal, Aldo P. Maggioni, Steven P. Marso, Peter Öhman, Neha J. Pagidipati, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F. Hernandez, Gary Wittert

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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.

LanguageEnglish
Pages1228-1239
Number of pages12
JournalNew England Journal of Medicine
Volume377
Issue number13
DOIs
Publication statusPublished - 28 Sep 2017

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Holman, R. R., Bethel, M. A., Mentz, R. J., Thompson, V. P., Lokhnygina, Y., Buse, J. B., ... Wittert, G. (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
Holman, Rury R. ; Bethel, M. Angelyn ; Mentz, Robert J. ; Thompson, Vivian P. ; Lokhnygina, Yuliya ; Buse, John B. ; Chan, Juliana C. ; Choi, Jasmine ; Gustavson, Stephanie M. ; Iqbal, Nayyar ; Maggioni, Aldo P. ; Marso, Steven P. ; Öhman, Peter ; Pagidipati, Neha J. ; Poulter, Neil ; Ramachandran, Ambady ; Zinman, Bernard ; Hernandez, Adrian F. ; Wittert, Gary. / Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 13. pp. 1228-1239.
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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.",
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Holman, RR, Bethel, MA, Mentz, RJ, Thompson, VP, Lokhnygina, Y, Buse, JB, Chan, JC, Choi, J, Gustavson, SM, Iqbal, N, Maggioni, AP, Marso, SP, Öhman, P, Pagidipati, NJ, Poulter, N, Ramachandran, A, Zinman, B, Hernandez, AF & Wittert, G 2017, 'Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes', New England Journal of Medicine, vol. 377, no. 13, pp. 1228-1239. https://doi.org/10.1056/NEJMoa1612917

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. / Holman, Rury R.; Bethel, M. Angelyn; Mentz, Robert J.; Thompson, Vivian P.; Lokhnygina, Yuliya; Buse, John B.; Chan, Juliana C.; Choi, Jasmine; Gustavson, Stephanie M.; Iqbal, Nayyar; Maggioni, Aldo P.; Marso, Steven P.; Öhman, Peter; Pagidipati, Neha J.; Poulter, Neil; Ramachandran, Ambady; Zinman, Bernard; Hernandez, Adrian F.; Wittert, Gary.

In: New England Journal of Medicine, Vol. 377, No. 13, 28.09.2017, p. 1228-1239.

Research output: Contribution to journalArticle

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T1 - Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

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 - Wittert, Gary

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.

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DO - 10.1056/NEJMoa1612917

M3 - Article

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JO - New England Journal of Medicine

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Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine. 2017 Sep 28;377(13):1228-1239. https://doi.org/10.1056/NEJMoa1612917