TY - JOUR
T1 - Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2-3 liraglutide clinical development studies
AU - Marso, Steven P.
AU - Lindsey, Jason B.
AU - Stolker, Joshua M.
AU - House, John A.
AU - Ravn, Gabriela Martinez
AU - Kennedy, Kevin F.
AU - Jensen, Troels M.
AU - Buse, John B.
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Diabetes mellitus
KW - Glucagon-like peptide-1
KW - Incretin
KW - Myocardial infarction
KW - Safety
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U2 - 10.1177/1479164111408937
DO - 10.1177/1479164111408937
M3 - Article
C2 - 21653676
AN - SCOPUS:80052039077
SN - 1479-1641
VL - 8
SP - 237
EP - 240
JO - Diabetes and Vascular Disease Research
JF - Diabetes and Vascular Disease Research
IS - 3
ER -