Liraglutide and cardiovascular outcomes in type 2 diabetes

LEADER Steering Committee on behalf of the LEADER Trial Investigators

Research output: Contribution to journalArticle

2252 Citations (Scopus)

Abstract

BACKGROUND The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P = 0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P = 0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P = 0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONS In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.

Original languageEnglish (US)
Pages (from-to)311-322
Number of pages12
JournalNew England Journal of Medicine
Volume375
Issue number4
DOIs
StatePublished - Jul 28 2016

Fingerprint

Type 2 Diabetes Mellitus
Placebos
Confidence Intervals
Cause of Death
Stroke
Myocardial Infarction
Liraglutide
Glucagon-Like Peptide 1
Random Allocation
Pancreatitis
Patient Care
Hospitalization
Heart Failure
Mortality
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

LEADER Steering Committee on behalf of the LEADER Trial Investigators (2016). Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine, 375(4), 311-322. https://doi.org/10.1056/NEJMoa1603827

Liraglutide and cardiovascular outcomes in type 2 diabetes. / LEADER Steering Committee on behalf of the LEADER Trial Investigators.

In: New England Journal of Medicine, Vol. 375, No. 4, 28.07.2016, p. 311-322.

Research output: Contribution to journalArticle

LEADER Steering Committee on behalf of the LEADER Trial Investigators 2016, 'Liraglutide and cardiovascular outcomes in type 2 diabetes', New England Journal of Medicine, vol. 375, no. 4, pp. 311-322. https://doi.org/10.1056/NEJMoa1603827
LEADER Steering Committee on behalf of the LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine. 2016 Jul 28;375(4):311-322. https://doi.org/10.1056/NEJMoa1603827
LEADER Steering Committee on behalf of the LEADER Trial Investigators. / Liraglutide and cardiovascular outcomes in type 2 diabetes. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 4. pp. 311-322.
@article{f3b982d20ba34642887b07545c2854c1,
title = "Liraglutide and cardiovascular outcomes in type 2 diabetes",
abstract = "BACKGROUND The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95{\%} confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0{\%}]) than in the placebo group (694 of 4672 [14.9{\%}]) (hazard ratio, 0.87; 95{\%} confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P = 0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7{\%}]) than in the placebo group (278 [6.0{\%}]) (hazard ratio, 0.78; 95{\%} CI, 0.66 to 0.93; P = 0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2{\%}]) than in the placebo group (447 [9.6{\%}]) (hazard ratio, 0.85; 95{\%} CI, 0.74 to 0.97; P = 0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONS In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.",
author = "{LEADER Steering Committee on behalf of the LEADER Trial Investigators} and Marso, {Steven P.} and Daniels, {Gilbert H.} and Frandsen, {Kirstine Brown} and Peter Kristensen and Mann, {Johannes F E} and Nauck, {Michael A.} and Nissen, {Steven E.} and Stuart Pocock and Poulter, {Neil R.} and Ravn, {Lasse S.} and Steinberg, {William M.} and Mette Stockner and Bernard Zinman and Bergenstal, {Richard M.} and Buse, {John B.}",
year = "2016",
month = "7",
day = "28",
doi = "10.1056/NEJMoa1603827",
language = "English (US)",
volume = "375",
pages = "311--322",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "4",

}

TY - JOUR

T1 - Liraglutide and cardiovascular outcomes in type 2 diabetes

AU - LEADER Steering Committee on behalf of the LEADER Trial Investigators

AU - Marso, Steven P.

AU - Daniels, Gilbert H.

AU - Frandsen, Kirstine Brown

AU - Kristensen, Peter

AU - Mann, Johannes F E

AU - Nauck, Michael A.

AU - Nissen, Steven E.

AU - Pocock, Stuart

AU - Poulter, Neil R.

AU - Ravn, Lasse S.

AU - Steinberg, William M.

AU - Stockner, Mette

AU - Zinman, Bernard

AU - Bergenstal, Richard M.

AU - Buse, John B.

PY - 2016/7/28

Y1 - 2016/7/28

N2 - BACKGROUND The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P = 0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P = 0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P = 0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONS In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.

AB - BACKGROUND The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P = 0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P = 0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P = 0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONS In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.

UR - http://www.scopus.com/inward/record.url?scp=84978839381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978839381&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1603827

DO - 10.1056/NEJMoa1603827

M3 - Article

C2 - 27295427

AN - SCOPUS:84978839381

VL - 375

SP - 311

EP - 322

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 4

ER -