Cardiovascular Risk Reduction With Liraglutide: An Exploratory Mediation Analysis of the LEADER Trial
Autor: | Stephen C. Bain, Richard E. Pratley, Steven E. Nissen, Tea Monk Fries, Michael A. Nauck, Martin Linder, Bernard Zinman, Neil R Poulter, David D. Ørsted, Johannes F.E. Mann, John B. Buse, Stuart J. Pocock |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Oncology
Male Endocrinology Diabetes and Metabolism Myocardial Infarction Type 2 diabetes law.invention chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial law Risk Factors Diabetic Nephropathies 030212 general & internal medicine Confounding Middle Aged Stroke Treatment Outcome Cardiovascular Diseases Female medicine.drug medicine.medical_specialty Mediation (statistics) Cardiovascular and Metabolic Risk 030209 endocrinology & metabolism 03 medical and health sciences Double-Blind Method Internal medicine Diabetes mellitus Internal Medicine medicine Humans Hypoglycemic Agents Renal Insufficiency Chronic Aged Advanced and Specialized Nursing Glycated Hemoglobin Mediation Analysis business.industry Liraglutide medicine.disease Hypoglycemia chemistry Diabetes Mellitus Type 2 Heart Disease Risk Factors Glycated hemoglobin business Mace Diabetic Angiopathies Follow-Up Studies |
Zdroj: | Diabetes Care |
ISSN: | 1935-5548 0149-5992 |
Popis: | OBJECTIVE The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial (ClinicalTrials.gov reg. no. NCT01179048) demonstrated a reduced risk of cardiovascular (CV) events for patients with type 2 diabetes who received the glucagon-like peptide 1 receptor agonist liraglutide versus placebo. The mechanisms behind this CV benefit remain unclear. We aimed to identify potential mediators for the CV benefit observed with liraglutide in the LEADER trial. RESEARCH DESIGN AND METHODS We performed exploratory analyses to identify potential mediators of the effect of liraglutide on major adverse CV events (MACE; composite of CV death, nonfatal myocardial infarction, or nonfatal stroke) from the following candidates: glycated hemoglobin (HbA1c), body weight, urinary albumin-to-creatinine ratio (UACR), confirmed hypoglycemia, sulfonylurea use, insulin use, systolic blood pressure, and LDL cholesterol. These candidates were selected as CV risk factors on which liraglutide had an effect in LEADER such that a reduction in CV risk might result. We used two methods based on a Cox proportional hazards model and the new Vansteelandt method designed to use all available information from the mediator and to control for confounding factors. RESULTS Analyses using the Cox methods and Vansteelandt method indicated potential mediation by HbA1c (up to 41% and 83% mediation, respectively) and UACR (up to 29% and 33% mediation, respectively) on the effect of liraglutide on MACE. Mediation effects were small for other candidates. CONCLUSIONS These analyses identify HbA1c and, to a lesser extent, UACR as potential mediators of the CV effects of liraglutide. Whether either is a marker of an unmeasured factor or a true mediator remains a key question that invites further investigation. |
Databáze: | OpenAIRE |
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