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LEADER: liraglutide and cardiovascular events in type 2 diabetes

A large trial of people with type 2 diabetes at high risk of heart and blood-vessel disease. Half took liraglutide and half took placebo, both on top of usual care. Fewer people on liraglutide had the combined event of a heart attack, a stroke or a heart-related death, and fewer died from any cause. Stomach and bowel side effects were the most common reason for stopping liraglutide.

Also called LEADER

  • Study
  • In this atlas

Overview

Design
Multicenter, international, randomized, double-blind, placebo-controlled trial with parallel groups (registry official title). The registry records phase 3 and double masking.
Phase
Phase 3
Enrolled
  • 9,341 participants (enrolled count) (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results, retrieved )
  • 9,340 patients (randomized count) (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes, retrieved )
Sponsor
Funder
Not recorded
Registry
  • NCT NCT01179048
Started
(actual) (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results, retrieved )
Primary completion
(actual) (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results, retrieved )
Completion
(actual) (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results, retrieved )
Results first posted
(actual) (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results, retrieved )
Countries
United States, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, Finland, France, Germany, Greece, India, Ireland, Israel, Italy, Mexico, Netherlands, Norway, Poland, Puerto Rico, Romania, Russia, Serbia, South Africa, South Korea, Spain, Sweden, Taiwan, United Arab Emirates, United Kingdom, Türkiye (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results, retrieved )
Care setting
Not reported
Registry status
  • “COMPLETED” (U.S. National Library of Medicine (ClinicalTrials.gov), retrieved )

Technical summary

Double-blind randomized trial sponsored by Novo Nordisk (NCT01179048). The primary hypothesis was noninferiority of liraglutide to placebo for the first death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke (margin 1.30 for the upper boundary of the 95% CI); 608 of 4668 patients on liraglutide and 694 of 4672 on placebo had the outcome (hazard ratio 0.87, 95% CI 0.78 to 0.97). Median follow-up 3.8 years. The registry counts 9341 enrolled; the paper reports 9340 randomized.

Arms

  • Liraglutide

    Intervention None named

    Liraglutide added to standard care. The sources read do not give the dose.

  • Placebo

    Intervention None named

    Placebo added to standard care.

Findings

No findings are published for this study.

Claims and evidence

Context Adults with type 2 diabetes and high cardiovascular risk (LEADER)

Recipient
Adult
Population
Patients with type 2 diabetes and high cardiovascular risk. The registry gives a minimum age of 50 years.
Care setting
Multicenter, international trial (registry official title). The care setting is not described further in the sources read.
Geography
Multinational. The registry lists the sites by country on the study page.
Life stage
Patients aged 50 years or older (registry minimum age 50 years)
Follow-up
Median follow-up 3.8 years.
Eligibility: 2 inclusion criteria; exclusion criteria not stated
Included
  • Type 2 diabetes
  • High cardiovascular risk
Excluded
None stated

  • Effect Interventional Certainty not assessed

    In LEADER, patients with type 2 diabetes and high cardiovascular risk were randomly assigned to liraglutide or placebo in addition to standard care. Over a median of 3.8 years, a first death from cardiovascular causes, nonfatal heart attack or nonfatal stroke occurred in 608 of 4668 patients (13.0%) on liraglutide and 694 of 4672 (14.9%) on placebo (hazard ratio 0.87, 95% CI 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Death from cardiovascular causes was lower, in 219 patients (4.7%) against 278 (6.0%) (hazard ratio 0.78, 95% CI 0.66 to 0.93), and so was death from any cause, in 381 (8.2%) against 447 (9.6%) (hazard ratio 0.85, 95% CI 0.74 to 0.97). Nonfatal heart attack, nonfatal stroke and hospitalization for heart failure were lower in the liraglutide group, but not by a significant margin. Gastrointestinal events were the most common adverse events that led to stopping liraglutide.

    Applies to Adult
    • Patients with type 2 diabetes and high cardiovascular risk. The registry gives a minimum age of 50 years.
    • Multicenter, international trial (registry official title). The care setting is not described further in the sources read.
    • Multinational. The registry lists the sites by country on the study page.
    • Patients aged 50 years or older (registry minimum age 50 years)
    Follow-up Median follow-up 3.8 years.
    Certainty method
    Not assessed
    Limitations
    The primary hypothesis was noninferiority of liraglutide to placebo, with a margin of 1.30; superiority was tested afterwards. The abstract says no adjustment for multiplicity was made for the prespecified exploratory outcomes. The registry counts 9341 enrolled and the paper 9340 randomized, a difference this atlas does not reconcile. Funded by Novo Nordisk and the National Institutes of Health (abstract). Only the PubMed abstract was read; the PMC copy is not in the open-access subset.
    Last checked
    2026-10-14
    Next evidence check due
    Not scheduled
    Sources and citations (6)

    1. Supports Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2016-07-28 · DOI: 10.1056/NEJMoa1603827 · PMID: 27295427 · PMCID: PMC4985288

      Locator
      Abstract, RESULTS, sentence 3
      How it applies
      Primary outcome counts by arm, hazard ratio and the noninferiority and superiority p-values.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      d86dca944a90d406ed7a98e6e46eb8d9774504c7746b167351df04f923325e26
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    2. Supports Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2016-07-28 · DOI: 10.1056/NEJMoa1603827 · PMID: 27295427 · PMCID: PMC4985288

      Locator
      Abstract, RESULTS, sentence 4; Abstract, RESULTS, sentence 5
      How it applies
      Cardiovascular death and all-cause death.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      d86dca944a90d406ed7a98e6e46eb8d9774504c7746b167351df04f923325e26
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    3. Supports Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2016-07-28 · DOI: 10.1056/NEJMoa1603827 · PMID: 27295427 · PMCID: PMC4985288

      Locator
      Abstract, RESULTS, sentence 6; Abstract, RESULTS, sentence 7; Abstract, RESULTS, sentence 8
      How it applies
      Outcomes that were not significantly different, and adverse events.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      d86dca944a90d406ed7a98e6e46eb8d9774504c7746b167351df04f923325e26
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    4. Supports Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2016-07-28 · DOI: 10.1056/NEJMoa1603827 · PMID: 27295427 · PMCID: PMC4985288

      Locator
      Abstract, RESULTS, sentence 1; Abstract, RESULTS, sentence 2
      How it applies
      Number randomized and median follow-up.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      d86dca944a90d406ed7a98e6e46eb8d9774504c7746b167351df04f923325e26
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    5. Background Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2016-07-28 · DOI: 10.1056/NEJMoa1603827 · PMID: 27295427 · PMCID: PMC4985288

      Locator
      Abstract, METHODS, sentence 1; Abstract, METHODS, sentence 2; Abstract, METHODS, sentence 3; Abstract, METHODS, sentence 4
      How it applies
      Design, primary outcome, noninferiority margin and multiplicity.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      d86dca944a90d406ed7a98e6e46eb8d9774504c7746b167351df04f923325e26
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    6. Background Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities. The full text and the version of record were not fetched. · Published 2016-07-28 · DOI: 10.1056/NEJMoa1603827 · PMID: 27295427 · PMCID: PMC4985288

      Locator
      Abstract, CONCLUSIONS, sentence 1; Abstract, CONCLUSIONS, sentence 2
      How it applies
      Conclusion and funding line.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      d86dca944a90d406ed7a98e6e46eb8d9774504c7746b167351df04f923325e26
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

Record details

Record id
cardio:leader-trial
Content hash
2ef40aaa28753b17151ff7e6d281176b953461a6809fa647d59cec52dcddb0c2