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Effect of linagliptin versus placebo on cardiovascular and kidney outcomes in nephrotic-range proteinuria and type 2 diabetes: the CARMELINA randomized controlled trial.
Abstract
<h4>Background</h4>Nephrotic-range proteinuria (NRP) is associated with rapid kidney
function loss and increased cardiovascular (CV) disease risk. We assessed the effects
of linagliptin (LINA) on CV and kidney outcomes in people with Type 2 diabetes (T2D)
with or without NRP.<h4>Methods</h4>Cardiovascular and renal microvascular outcome
study with LINA randomized participants with T2D and CV disease and/or kidney disease
to LINA 5 mg or placebo (PBO). The primary endpoint [time to first occurrence of 3-point
major adverse cardiac events (3P-MACE)], and kidney outcomes, were evaluated by NRP
status [urinary albumin:creatinine ratio (UACR) ≥2200 mg/g] at baseline (BL) in participants
treated with one or more dose of study medication.<h4>Results</h4>NRP was present
in 646/6979 [9.3% (LINA/PBO n = 317/n = 329); median UACR 3486 (Q1: 2746/Q3: 4941) mg/g] participants, who compared with
no-NRP were younger (62.3/66.1 years) and had lower estimated glomerular filtration
rate (eGFR) (39.9/56.1 mL/min/1.73 m2). Over a median of 2.2 years, 3P-MACE occurred with a 2.0-fold higher rate in NRP
versus no-NRP (PBO group), with a neutral LINA effect, regardless of NRP. The composite
of time to renal death, end-stage kidney disease (ESKD) or decrease of ≥40 or ≥50%
in eGFR, occurred with 12.3- and 13.6-fold higher rate with NRP (PBO group); evidence
of heterogeneity of effects with LINA was observed for the former [NRP yes/no: hazard
ratio 0.80 (0.63-1.01)/1.25 (1.02-1.54); P-interaction 0.005], but not the latter
[0.83 (0.64-1.09)/1.17 (0.91-1.51), P-interaction 0.07]. No heterogeneity was observed
for renal death or ESKD [0.88 (0.64-1.21)/0.94 (0.67-1.31), P-interaction 0.79]. Glycated
haemoglobin A1c (HbA1c) was significantly reduced regardless of NRP, without increasing
hypoglycaemia risk. Regression to normoalbuminuria [1.20 (1.07-1.34)] and reduction
of UACR ≥50% [1.15 (1.07-1.25)] from BL, occurred more frequently with LINA, regardless
of NRP status (P-interactions >0.05).<h4>Conclusions</h4>Individuals with T2D and
NRP have a high disease burden. LINA reduces their albuminuria burden and HbA1c, without
affecting CV or kidney risk.
Type
Journal articleSubject
CARMELINA investigatorsPermalink
https://hdl.handle.net/10161/22861Published Version (Please cite this version)
10.1093/ckj/sfaa225Publication Info
Wanner, Christoph; Cooper, Mark E; Johansen, Odd Erik; Toto, Robert; Rosenstock, Julio;
McGuire, Darren K; ... CARMELINA investigators (2021). Effect of linagliptin versus placebo on cardiovascular and kidney outcomes in nephrotic-range
proteinuria and type 2 diabetes: the CARMELINA randomized controlled trial. Clinical kidney journal, 14(1). pp. 226-236. 10.1093/ckj/sfaa225. Retrieved from https://hdl.handle.net/10161/22861.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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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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