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
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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