title: Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies.
abstract: We assessed the cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist, using existing clinical data. Patient-level results from all completed phase 2 and 3 studies from the liraglutide clinical development programme were pooled to determine rates of major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, stroke. MACE were identified by querying the study database using Medical Dictionary for Regulatory Activities (MedDRA) terms combined with serious adverse events recorded by study investigators. Broad, narrow, and custom groups of MedDRA queries were used. Candidate events from each query were independently adjudicated post hoc. In 15 studies (6638 patients; 4257 liraglutide treated), there were 114 patients with MACE identified using the broad MedDRA query. Of these, 44 were classified as serious adverse events and 39 were adjudicated as MACE. The incidence ratio for adjudicated broad/serious MACE associated with liraglutide was 0.73 (95% CI 0.38-1.41) versus all comparator drugs (metformin, glimepiride, rosiglitazone, insulin glargine, placebo), within cardiovascular safety limits defined by the United States Food & Drug Administration for diabetes therapies under current investigation.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Marso
authors.forename: Jason B
authors.initials: JB
authors.lastname: Lindsey
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Stolker
authors.forename: John A
authors.initials: JA
authors.lastname: House
authors.forename: Gabriela
authors.initials: G
authors.lastname: Martinez Ravn
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Kennedy
authors.forename: Troels M
authors.initials: TM
authors.lastname: Jensen
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000401:mortality; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D019317:Evidence-Based Medicine; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D015994:Incidence; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1