Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke

Subodh Verma, Neil R. Poulter, Deepak L. Bhatt, Stephen C. Bain, John B. Buse, Lawrence A. Leiter, Michael A. Nauck, Richard E. Pratley, Bernard Zinman, David D. Ørsted, Tea Monk Fries, Søren Rasmussen, Steven P Marso

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

BACKGROUND: The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and/or stroke. METHODS: LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI/stroke, established atherosclerotic cardiovascular disease without MI/stroke, or cardiovascular risk factors alone. RESULTS: Of the 9340 patients, 3692 (39.5%) had a history of MI/stroke, 3083 (33.0%) had established atherosclerotic cardiovascular disease without MI/stroke, and 2565 (27.5%) had risk factors alone. Major adverse cardiovascular events occurred in 18.8% of patients with a history of MI/stroke (incidence rate, 5.0 per 100 patient-years), 11.6% of patients with established atherosclerotic cardiovascular disease without MI/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8% of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI/stroke (322 of 1865 [17.3%] versus 372 of 1827 patients [20.4%]; hazard ratio, 0.85; 95% CI, 0.73-0.99) and in those with established atherosclerotic cardiovascular disease without MI/stroke (158 of 1538 [10.3%] versus 199 of 1545 patients [12.9%]; hazard ratio, 0.76; 95% CI, 0.62-0.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95% CI, 0.84-1.38, Pinteraction=0.11). Similar results were seen for secondary outcomes across risk groups. CONCLUSIONS: In this post hoc analysis of patients with type 2 diabetes mellitus and high cardiovascular risk, liraglutide reduced cardiovascular outcomes both in patients with a history of MI/stroke and in those with established atherosclerotic cardiovascular disease without MI/stroke. The cardiovascular effect appeared neutral in patients with cardiovascular risk factors alone. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01179048.

Original languageEnglish (US)
Pages (from-to)2884-2894
Number of pages11
JournalCirculation
Volume138
Issue number25
DOIs
StatePublished - Dec 18 2018

Fingerprint

Type 2 Diabetes Mellitus
Stroke
Myocardial Infarction
Cardiovascular Diseases
Liraglutide
Placebos
Incidence
Glucagon-Like Peptide 1
Maximum Tolerated Dose

Keywords

  • cardiovascular system
  • diabetes mellitus
  • glucagon-like peptide-1
  • liraglutide
  • randomized controlled trial as topic
  • type 2

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke. / Verma, Subodh; Poulter, Neil R.; Bhatt, Deepak L.; Bain, Stephen C.; Buse, John B.; Leiter, Lawrence A.; Nauck, Michael A.; Pratley, Richard E.; Zinman, Bernard; Ørsted, David D.; Monk Fries, Tea; Rasmussen, Søren; Marso, Steven P.

In: Circulation, Vol. 138, No. 25, 18.12.2018, p. 2884-2894.

Research output: Contribution to journalArticle

Verma, S, Poulter, NR, Bhatt, DL, Bain, SC, Buse, JB, Leiter, LA, Nauck, MA, Pratley, RE, Zinman, B, Ørsted, DD, Monk Fries, T, Rasmussen, S & Marso, SP 2018, 'Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke', Circulation, vol. 138, no. 25, pp. 2884-2894. https://doi.org/10.1161/CIRCULATIONAHA.118.034516
Verma, Subodh ; Poulter, Neil R. ; Bhatt, Deepak L. ; Bain, Stephen C. ; Buse, John B. ; Leiter, Lawrence A. ; Nauck, Michael A. ; Pratley, Richard E. ; Zinman, Bernard ; Ørsted, David D. ; Monk Fries, Tea ; Rasmussen, Søren ; Marso, Steven P. / Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke. In: Circulation. 2018 ; Vol. 138, No. 25. pp. 2884-2894.
@article{1bf21b02b14b49c28ac67942d2c46e4c,
title = "Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke",
abstract = "BACKGROUND: The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and/or stroke. METHODS: LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI/stroke, established atherosclerotic cardiovascular disease without MI/stroke, or cardiovascular risk factors alone. RESULTS: Of the 9340 patients, 3692 (39.5{\%}) had a history of MI/stroke, 3083 (33.0{\%}) had established atherosclerotic cardiovascular disease without MI/stroke, and 2565 (27.5{\%}) had risk factors alone. Major adverse cardiovascular events occurred in 18.8{\%} of patients with a history of MI/stroke (incidence rate, 5.0 per 100 patient-years), 11.6{\%} of patients with established atherosclerotic cardiovascular disease without MI/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8{\%} of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI/stroke (322 of 1865 [17.3{\%}] versus 372 of 1827 patients [20.4{\%}]; hazard ratio, 0.85; 95{\%} CI, 0.73-0.99) and in those with established atherosclerotic cardiovascular disease without MI/stroke (158 of 1538 [10.3{\%}] versus 199 of 1545 patients [12.9{\%}]; hazard ratio, 0.76; 95{\%} CI, 0.62-0.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95{\%} CI, 0.84-1.38, Pinteraction=0.11). Similar results were seen for secondary outcomes across risk groups. CONCLUSIONS: In this post hoc analysis of patients with type 2 diabetes mellitus and high cardiovascular risk, liraglutide reduced cardiovascular outcomes both in patients with a history of MI/stroke and in those with established atherosclerotic cardiovascular disease without MI/stroke. The cardiovascular effect appeared neutral in patients with cardiovascular risk factors alone. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01179048.",
keywords = "cardiovascular system, diabetes mellitus, glucagon-like peptide-1, liraglutide, randomized controlled trial as topic, type 2",
author = "Subodh Verma and Poulter, {Neil R.} and Bhatt, {Deepak L.} and Bain, {Stephen C.} and Buse, {John B.} and Leiter, {Lawrence A.} and Nauck, {Michael A.} and Pratley, {Richard E.} and Bernard Zinman and {\O}rsted, {David D.} and {Monk Fries}, Tea and S{\o}ren Rasmussen and Marso, {Steven P}",
year = "2018",
month = "12",
day = "18",
doi = "10.1161/CIRCULATIONAHA.118.034516",
language = "English (US)",
volume = "138",
pages = "2884--2894",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "25",

}

TY - JOUR

T1 - Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke

AU - Verma, Subodh

AU - Poulter, Neil R.

AU - Bhatt, Deepak L.

AU - Bain, Stephen C.

AU - Buse, John B.

AU - Leiter, Lawrence A.

AU - Nauck, Michael A.

AU - Pratley, Richard E.

AU - Zinman, Bernard

AU - Ørsted, David D.

AU - Monk Fries, Tea

AU - Rasmussen, Søren

AU - Marso, Steven P

PY - 2018/12/18

Y1 - 2018/12/18

N2 - BACKGROUND: The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and/or stroke. METHODS: LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI/stroke, established atherosclerotic cardiovascular disease without MI/stroke, or cardiovascular risk factors alone. RESULTS: Of the 9340 patients, 3692 (39.5%) had a history of MI/stroke, 3083 (33.0%) had established atherosclerotic cardiovascular disease without MI/stroke, and 2565 (27.5%) had risk factors alone. Major adverse cardiovascular events occurred in 18.8% of patients with a history of MI/stroke (incidence rate, 5.0 per 100 patient-years), 11.6% of patients with established atherosclerotic cardiovascular disease without MI/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8% of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI/stroke (322 of 1865 [17.3%] versus 372 of 1827 patients [20.4%]; hazard ratio, 0.85; 95% CI, 0.73-0.99) and in those with established atherosclerotic cardiovascular disease without MI/stroke (158 of 1538 [10.3%] versus 199 of 1545 patients [12.9%]; hazard ratio, 0.76; 95% CI, 0.62-0.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95% CI, 0.84-1.38, Pinteraction=0.11). Similar results were seen for secondary outcomes across risk groups. CONCLUSIONS: In this post hoc analysis of patients with type 2 diabetes mellitus and high cardiovascular risk, liraglutide reduced cardiovascular outcomes both in patients with a history of MI/stroke and in those with established atherosclerotic cardiovascular disease without MI/stroke. The cardiovascular effect appeared neutral in patients with cardiovascular risk factors alone. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01179048.

AB - BACKGROUND: The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and/or stroke. METHODS: LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI/stroke, established atherosclerotic cardiovascular disease without MI/stroke, or cardiovascular risk factors alone. RESULTS: Of the 9340 patients, 3692 (39.5%) had a history of MI/stroke, 3083 (33.0%) had established atherosclerotic cardiovascular disease without MI/stroke, and 2565 (27.5%) had risk factors alone. Major adverse cardiovascular events occurred in 18.8% of patients with a history of MI/stroke (incidence rate, 5.0 per 100 patient-years), 11.6% of patients with established atherosclerotic cardiovascular disease without MI/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8% of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI/stroke (322 of 1865 [17.3%] versus 372 of 1827 patients [20.4%]; hazard ratio, 0.85; 95% CI, 0.73-0.99) and in those with established atherosclerotic cardiovascular disease without MI/stroke (158 of 1538 [10.3%] versus 199 of 1545 patients [12.9%]; hazard ratio, 0.76; 95% CI, 0.62-0.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95% CI, 0.84-1.38, Pinteraction=0.11). Similar results were seen for secondary outcomes across risk groups. CONCLUSIONS: In this post hoc analysis of patients with type 2 diabetes mellitus and high cardiovascular risk, liraglutide reduced cardiovascular outcomes both in patients with a history of MI/stroke and in those with established atherosclerotic cardiovascular disease without MI/stroke. The cardiovascular effect appeared neutral in patients with cardiovascular risk factors alone. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01179048.

KW - cardiovascular system

KW - diabetes mellitus

KW - glucagon-like peptide-1

KW - liraglutide

KW - randomized controlled trial as topic

KW - type 2

UR - http://www.scopus.com/inward/record.url?scp=85058870723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058870723&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.118.034516

DO - 10.1161/CIRCULATIONAHA.118.034516

M3 - Article

C2 - 30566004

AN - SCOPUS:85058870723

VL - 138

SP - 2884

EP - 2894

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 25

ER -