Effects of Linagliptin on Cardiovascular and Kidney Outcomes in People With Normal and Reduced Kidney Function: Secondary Analysis of the CARMELINA Randomized Trial.
Abstract
<h4>Objective</h4>Type 2 diabetes is a leading cause of kidney failure, but few outcome
trials proactively enrolled individuals with chronic kidney disease (CKD). We performed
secondary analyses of cardiovascular (CV) and kidney outcomes across baseline estimated
glomerular filtration rate (eGFR) categories (≥60, 45 to <60, 30 to <45, and <30 mL/min/1.73
m<sup>2</sup>) in Cardiovascular and Renal Microvascular Outcome Study With Linagliptin
(CARMELINA), a cardiorenal placebo-controlled outcome trial of the dipeptidyl peptidase
4 inhibitor linagliptin (NCT01897532).<h4>Research design and methods</h4>Participants
with CV disease and/or CKD were included. The primary outcome was time to first occurrence
of CV death, nonfatal myocardial infarction, or nonfatal stroke (three-point major
adverse CV event [3P-MACE]), with a secondary outcome of renal death, end-stage kidney
disease, or sustained ≥40% decrease in eGFR from baseline. Other end points included
progression of albuminuria, change in HbA1c, and adverse events (AEs) including hypoglycemia.<h4>Results</h4>A total of 6,979
subjects (mean age 65.9 years; eGFR 54.6 mL/min/1.73 m2; 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin
as compared with placebo did not affect the risk for 3P-MACE (hazard ratio 1.02 [95%
CI 0.89, 1.17]) or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction P values >0.05). Regardless of eGFR, albuminuria progression was reduced with linagliptin,
as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced among groups overall
and across eGFR categories.<h4>Conclusions</h4>Across all GFR categories, in participants
with type 2 diabetes and CKD and/or CV disease, there was no difference in risk for
linagliptin versus placebo on CV and kidney events. Significant reductions in risk
for albuminuria progression and HbA1c and no difference in AEs were observed.
Type
Journal articleSubject
CARMELINA investigatorsKidney
Cardiovascular System
Humans
Diabetic Nephropathies
Kidney Failure, Chronic
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Hypoglycemic Agents
Glomerular Filtration Rate
Prognosis
Treatment Outcome
Incidence
Mortality
Retrospective Studies
Aged
Middle Aged
Female
Male
Renal Insufficiency, Chronic
Dipeptidyl-Peptidase IV Inhibitors
Linagliptin
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https://hdl.handle.net/10161/22866Published Version (Please cite this version)
10.2337/dc20-0279Publication Info
Perkovic, Vlado; Toto, Robert; Cooper, Mark E; Mann, Johannes FE; Rosenstock, Julio;
McGuire, Darren K; ... CARMELINA investigators (2020). Effects of Linagliptin on Cardiovascular and Kidney Outcomes in People With Normal
and Reduced Kidney Function: Secondary Analysis of the CARMELINA Randomized Trial.
Diabetes care, 43(8). pp. 1803-1812. 10.2337/dc20-0279. Retrieved from https://hdl.handle.net/10161/22866.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
John Hunter Peel Alexander
Professor of Medicine
John H. Alexander, MD, MHS is a cardiologist and Professor of Medicine in the Department
of Medicine, Division of Cardiology at Duke University School of Medicine, as well
as the Vice Chief, Clinical Research in the Division of Cardiology. He is the Director
of Cardiovascular Research at the Duke Clinical Research Institute where he oversees
a large group of clinical research faculty and a broad portfolio of cardiovascular
clinical trials and observational clinical research programs. He is a

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