{ "release_id": "f6f6f1b6f50379ed", "id": "cardio:leader-trial", "owner": "cardio", "kind": "study", "slug": "leader-trial", "name": "LEADER: liraglutide and cardiovascular events in type 2 diabetes", "aliases": [ "LEADER" ], "atlases": [ "cardio" ], "summary_plain": "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.", "summary_technical": "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.", "editorial_state": "draft", "last_substantive_edit": "2026-10-14", "last_evidence_check": null, "next_review_due": null, "identifiers": [ { "scheme": "nct", "value": "NCT01179048", "normalized_value": "NCT01179048", "match": "exact", "version": null, "label": null, "from_source": false } ], "navigation": { "cardio": { "system": [ "metabolism" ], "condition-area": [ "diabetes-and-metabolic-disease" ] } }, "payload": { "design": "Multicenter, international, randomized, double-blind, placebo-controlled trial with parallel groups (registry official title). The registry records phase 3 and double masking.", "drug_phase": "3", "registry_statuses": [ { "status": "COMPLETED", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" } ], "start_date": { "date": "2010-08-31", "type": "actual", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, "primary_completion_date": { "date": "2015-12-17", "type": "actual", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, "completion_date": { "date": "2015-12-17", "type": "actual", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, "results_first_posted": { "date": "2017-03-01", "type": "actual", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, "countries": [ { "code": "US", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "AU", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "AT", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "BE", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "BR", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "CA", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "CN", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "CZ", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "DK", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "FI", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "FR", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "DE", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "GR", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "IN", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "IE", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "IL", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "IT", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "MX", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "NL", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "NO", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "PL", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "PR", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "RO", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "RU", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "RS", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "ZA", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "KR", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "ES", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "SE", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "TW", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "AE", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "GB", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "code": "TR", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" } ], "care_setting": null, "stopped_early": null, "enrollment": [ { "count": 9341, "basis": "enrolled", "unit": "participants", "snapshot": "cardio:ctgov-nct01179048-2026-10-14" }, { "count": 9340, "basis": "randomized", "unit": "patients", "snapshot": "cardio:pubmed-27295427-2026-10-14" } ], "arms": [ { "id": "cardio:leader-arm-liraglutide", "label": "Liraglutide", "intervention": null, "description": "Liraglutide added to standard care. The sources read do not give the dose." }, { "id": "cardio:leader-arm-placebo", "label": "Placebo", "intervention": null, "description": "Placebo added to standard care." } ], "findings": [] }, "content_digest": "2ef40aaa28753b17151ff7e6d281176b953461a6809fa647d59cec52dcddb0c2", "review": { "content_digest": "2ef40aaa28753b17151ff7e6d281176b953461a6809fa647d59cec52dcddb0c2", "current": [], "conflicting": [], "stale": [], "inactive": [] }, "claims": [ { "release_id": "f6f6f1b6f50379ed", "id": "cardio:claim-leader-primary-effect", "owner": "cardio", "subject_entity_id": "cardio:leader-trial", "category": "effect", "statement": "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.", "context": { "id": "cardio:ctx-leader-adults-type-2-diabetes-high-cv-risk", "label": "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_note": "Patients aged 50 years or older (registry minimum age 50 years)", "life_stage_terms": null, "gestational_age_min_days": null, "gestational_age_max_days": null, "gestational_age_basis": null, "postnatal_age_min_days": null, "postnatal_age_max_days": null, "gestational_age_status": null, "postnatal_age_status": null, "followup_description": "Median follow-up 3.8 years.", "eligibility": { "inclusion": [ "Type 2 diabetes", "High cardiovascular risk" ], "exclusion": [] } }, "evidence_stage": "interventional", "certainty": "not_assessed", "certainty_method": null, "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.", "editorial_state": "draft", "checked_at": "2026-10-14", "next_review_due": null, "valid_from": null, "valid_to": null, "citations": [ { "evidence_role": "supports", "locator": "Abstract, RESULTS, sentence 3", "applicability_note": "Primary outcome counts by arm, hazard ratio and the noninferiority and superiority p-values.", "snapshot": { "id": "cardio:pubmed-27295427-2026-10-14", "retrieved_at": "2026-10-14T18:18:48Z", "content_hash": "d86dca944a90d406ed7a98e6e46eb8d9774504c7746b167351df04f923325e26", "source_effective_date": null, "public_archive_url": null, "source_state": "current" }, "source": { "id": "cardio:pubmed-10-1056-nejmoa1603827", "source_type": "publication", "title": "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes", "canonical_url": "https://doi.org/10.1056/NEJMoa1603827", "identifiers": [ { "scheme": "doi", "value": "10.1056/NEJMoa1603827", "normalized_value": "10.1056/nejmoa1603827", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmid", "value": "27295427", "normalized_value": "27295427", "match": "exact", "version": null, "label": null, "from_source": false }, { "scheme": "pmcid", "value": "PMC4985288", "normalized_value": "PMC4985288", "match": "exact", "version": null, "label": null, "from_source": false } ], "publication_date": "2016-07-28", "publisher": "The New England journal of medicine", "edition": "PubMed record (abstract and bibliographic data) from NCBI E-utilities. 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