Cargando…

Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis

AIMS: To investigate whether effects on chronic kidney disease risk factors could explain the apparent reduction in kidney outcomes (composite of macroalbuminuria, doubling of serum creatinine, renal replacement therapy, or renal death), primarily driven by changes in albuminuria, after treatment wi...

Descripción completa

Detalles Bibliográficos
Autores principales: Mann, Johannes F. E., Buse, John B., Idorn, Thomas, Leiter, Lawrence A., Pratley, Richard E., Rasmussen, Søren, Vilsbøll, Tina, Wolthers, Benjamin, Perkovic, Vlado
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453827/
https://www.ncbi.nlm.nih.gov/pubmed/34009708
http://dx.doi.org/10.1111/dom.14443
_version_ 1784570354984812544
author Mann, Johannes F. E.
Buse, John B.
Idorn, Thomas
Leiter, Lawrence A.
Pratley, Richard E.
Rasmussen, Søren
Vilsbøll, Tina
Wolthers, Benjamin
Perkovic, Vlado
author_facet Mann, Johannes F. E.
Buse, John B.
Idorn, Thomas
Leiter, Lawrence A.
Pratley, Richard E.
Rasmussen, Søren
Vilsbøll, Tina
Wolthers, Benjamin
Perkovic, Vlado
author_sort Mann, Johannes F. E.
collection PubMed
description AIMS: To investigate whether effects on chronic kidney disease risk factors could explain the apparent reduction in kidney outcomes (composite of macroalbuminuria, doubling of serum creatinine, renal replacement therapy, or renal death), primarily driven by changes in albuminuria, after treatment with the glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) liraglutide and semaglutide in patients with type 2 diabetes in the LEADER and SUSTAIN 6 trials. MATERIALS AND METHODS: We evaluated the mediation effect of glycated haemoglobin (HbA1c), systolic blood pressure (BP), and body weight on the kidney effects of GLP‐1RAs. Diastolic BP, haemoglobin, heart rate, low‐density lipoprotein and total cholesterol, and white blood cell count were also investigated. The mediation effect was estimated by the novel Vansteelandt statistical method. Subgroups with estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m(2) were examined in LEADER. RESULTS: We observed that HbA1c mediated 25% (95% confidence interval [CI] −7.1; 67.3) and 26% (95% CI noncalculable), and systolic BP 9% (95% CI 2.8; 22.7) and 22% (95% CI noncalculable) of kidney effects of GLP‐1RAs in LEADER and SUSTAIN 6, respectively. Small or no mediation was observed for the other parameters; for example, body weight mediated 9% (95% CI −7.9; 35.5) in the former and did not mediate effects in the latter study. Mediation by HbA1c was greater in patients with eGFR ≥60 mL/min/1.73 m(2) (57%) versus those with eGFR <60 mL/min/1.73 m(2) (no mediation). CONCLUSIONS: Our results suggest that HbA1c and systolic BP may moderately mediate kidney benefits of liraglutide and semaglutide, with all other variables having a small to no effect. Potential kidney benefits may be driven by other mediators or potentially by direct mechanisms.
format Online
Article
Text
id pubmed-8453827
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-84538272021-09-27 Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis Mann, Johannes F. E. Buse, John B. Idorn, Thomas Leiter, Lawrence A. Pratley, Richard E. Rasmussen, Søren Vilsbøll, Tina Wolthers, Benjamin Perkovic, Vlado Diabetes Obes Metab Original Articles AIMS: To investigate whether effects on chronic kidney disease risk factors could explain the apparent reduction in kidney outcomes (composite of macroalbuminuria, doubling of serum creatinine, renal replacement therapy, or renal death), primarily driven by changes in albuminuria, after treatment with the glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) liraglutide and semaglutide in patients with type 2 diabetes in the LEADER and SUSTAIN 6 trials. MATERIALS AND METHODS: We evaluated the mediation effect of glycated haemoglobin (HbA1c), systolic blood pressure (BP), and body weight on the kidney effects of GLP‐1RAs. Diastolic BP, haemoglobin, heart rate, low‐density lipoprotein and total cholesterol, and white blood cell count were also investigated. The mediation effect was estimated by the novel Vansteelandt statistical method. Subgroups with estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m(2) were examined in LEADER. RESULTS: We observed that HbA1c mediated 25% (95% confidence interval [CI] −7.1; 67.3) and 26% (95% CI noncalculable), and systolic BP 9% (95% CI 2.8; 22.7) and 22% (95% CI noncalculable) of kidney effects of GLP‐1RAs in LEADER and SUSTAIN 6, respectively. Small or no mediation was observed for the other parameters; for example, body weight mediated 9% (95% CI −7.9; 35.5) in the former and did not mediate effects in the latter study. Mediation by HbA1c was greater in patients with eGFR ≥60 mL/min/1.73 m(2) (57%) versus those with eGFR <60 mL/min/1.73 m(2) (no mediation). CONCLUSIONS: Our results suggest that HbA1c and systolic BP may moderately mediate kidney benefits of liraglutide and semaglutide, with all other variables having a small to no effect. Potential kidney benefits may be driven by other mediators or potentially by direct mechanisms. Blackwell Publishing Ltd 2021-06-01 2021-09 /pmc/articles/PMC8453827/ /pubmed/34009708 http://dx.doi.org/10.1111/dom.14443 Text en © 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Mann, Johannes F. E.
Buse, John B.
Idorn, Thomas
Leiter, Lawrence A.
Pratley, Richard E.
Rasmussen, Søren
Vilsbøll, Tina
Wolthers, Benjamin
Perkovic, Vlado
Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis
title Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis
title_full Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis
title_fullStr Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis
title_full_unstemmed Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis
title_short Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis
title_sort potential kidney protection with liraglutide and semaglutide: exploratory mediation analysis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453827/
https://www.ncbi.nlm.nih.gov/pubmed/34009708
http://dx.doi.org/10.1111/dom.14443
work_keys_str_mv AT mannjohannesfe potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis
AT busejohnb potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis
AT idornthomas potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis
AT leiterlawrencea potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis
AT pratleyricharde potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis
AT rasmussensøren potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis
AT vilsbølltina potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis
AT wolthersbenjamin potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis
AT perkovicvlado potentialkidneyprotectionwithliraglutideandsemaglutideexploratorymediationanalysis