Cargando…

Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials

BACKGROUND: Exploratory analysis to determine the effect of semaglutide versus comparators on high-sensitivity C-reactive protein (hsCRP) in subjects with type 2 diabetes. METHODS: Trials of once-weekly subcutaneous (SUSTAIN 3) and once-daily oral (PIONEER 1, 2, 5) semaglutide with hsCRP data were a...

Descripción completa

Detalles Bibliográficos
Autores principales: Mosenzon, Ofri, Capehorn, Matthew S., De Remigis, Alessandra, Rasmussen, Søren, Weimers, Petra, Rosenstock, Julio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440529/
https://www.ncbi.nlm.nih.gov/pubmed/36056351
http://dx.doi.org/10.1186/s12933-022-01585-7
_version_ 1784782372531601408
author Mosenzon, Ofri
Capehorn, Matthew S.
De Remigis, Alessandra
Rasmussen, Søren
Weimers, Petra
Rosenstock, Julio
author_facet Mosenzon, Ofri
Capehorn, Matthew S.
De Remigis, Alessandra
Rasmussen, Søren
Weimers, Petra
Rosenstock, Julio
author_sort Mosenzon, Ofri
collection PubMed
description BACKGROUND: Exploratory analysis to determine the effect of semaglutide versus comparators on high-sensitivity C-reactive protein (hsCRP) in subjects with type 2 diabetes. METHODS: Trials of once-weekly subcutaneous (SUSTAIN 3) and once-daily oral (PIONEER 1, 2, 5) semaglutide with hsCRP data were analyzed. Subjects with type 2 diabetes (N = 2482) received semaglutide (n = 1328) or comparators (placebo, n = 339; exenatide extended-release, n = 405; empagliflozin, n = 410). hsCRP ratio to baseline at end-of-treatment was analyzed overall, by clinical cutoff (< 1.0, ≥ 1.0 to ≤ 3.0, or > 3.0 mg/L), by tertile, and by estimated glomerular filtration rate in PIONEER 5 (a trial which was conducted in a population with type 2 diabetes and chronic kidney disease [CKD]). Mediation analyses assessed the effect of change in glycated hemoglobin (HbA(1c)) and/or change in body weight (BW) on hsCRP reductions. RESULTS: Geometric mean baseline hsCRP was similar across trials (range 2.7–3.0 mg/L). Semaglutide reduced hsCRP levels by clinical cutoffs and tertiles from baseline to end-of-treatment in all trials versus comparators (estimated treatment ratios [ETRs] versus comparators: 0.70–0.76; p < 0.01) except versus placebo in PIONEER 5 (ETR [95% CI]: 0.83 [0.67–1.03]; p > 0.05). The effect of semaglutide on hsCRP was partially mediated (20.6–61.8%) by change in HbA(1c) and BW. CONCLUSIONS: Semaglutide reduced hsCRP ratios-to-baseline versus comparators in subjects with type 2 diabetes (not significant with CKD). This effect was partially mediated via reductions in HbA(1c) and BW and potentially by a direct effect of semaglutide. Semaglutide appears to have an anti-inflammatory effect, which is being further investigated in ongoing trials. Trial registrations: ClinicalTrials.gov identifiers: NCT01885208 (first registered June 2013), NCT02906930 (first registered September 2016), NCT02863328 (first registered August 2016), NCT02827708 (first registered July 2016). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01585-7.
format Online
Article
Text
id pubmed-9440529
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-94405292022-09-04 Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials Mosenzon, Ofri Capehorn, Matthew S. De Remigis, Alessandra Rasmussen, Søren Weimers, Petra Rosenstock, Julio Cardiovasc Diabetol Research BACKGROUND: Exploratory analysis to determine the effect of semaglutide versus comparators on high-sensitivity C-reactive protein (hsCRP) in subjects with type 2 diabetes. METHODS: Trials of once-weekly subcutaneous (SUSTAIN 3) and once-daily oral (PIONEER 1, 2, 5) semaglutide with hsCRP data were analyzed. Subjects with type 2 diabetes (N = 2482) received semaglutide (n = 1328) or comparators (placebo, n = 339; exenatide extended-release, n = 405; empagliflozin, n = 410). hsCRP ratio to baseline at end-of-treatment was analyzed overall, by clinical cutoff (< 1.0, ≥ 1.0 to ≤ 3.0, or > 3.0 mg/L), by tertile, and by estimated glomerular filtration rate in PIONEER 5 (a trial which was conducted in a population with type 2 diabetes and chronic kidney disease [CKD]). Mediation analyses assessed the effect of change in glycated hemoglobin (HbA(1c)) and/or change in body weight (BW) on hsCRP reductions. RESULTS: Geometric mean baseline hsCRP was similar across trials (range 2.7–3.0 mg/L). Semaglutide reduced hsCRP levels by clinical cutoffs and tertiles from baseline to end-of-treatment in all trials versus comparators (estimated treatment ratios [ETRs] versus comparators: 0.70–0.76; p < 0.01) except versus placebo in PIONEER 5 (ETR [95% CI]: 0.83 [0.67–1.03]; p > 0.05). The effect of semaglutide on hsCRP was partially mediated (20.6–61.8%) by change in HbA(1c) and BW. CONCLUSIONS: Semaglutide reduced hsCRP ratios-to-baseline versus comparators in subjects with type 2 diabetes (not significant with CKD). This effect was partially mediated via reductions in HbA(1c) and BW and potentially by a direct effect of semaglutide. Semaglutide appears to have an anti-inflammatory effect, which is being further investigated in ongoing trials. Trial registrations: ClinicalTrials.gov identifiers: NCT01885208 (first registered June 2013), NCT02906930 (first registered September 2016), NCT02863328 (first registered August 2016), NCT02827708 (first registered July 2016). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01585-7. BioMed Central 2022-09-02 /pmc/articles/PMC9440529/ /pubmed/36056351 http://dx.doi.org/10.1186/s12933-022-01585-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Mosenzon, Ofri
Capehorn, Matthew S.
De Remigis, Alessandra
Rasmussen, Søren
Weimers, Petra
Rosenstock, Julio
Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials
title Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials
title_full Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials
title_fullStr Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials
title_full_unstemmed Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials
title_short Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials
title_sort impact of semaglutide on high-sensitivity c-reactive protein: exploratory patient-level analyses of sustain and pioneer randomized clinical trials
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440529/
https://www.ncbi.nlm.nih.gov/pubmed/36056351
http://dx.doi.org/10.1186/s12933-022-01585-7
work_keys_str_mv AT mosenzonofri impactofsemaglutideonhighsensitivitycreactiveproteinexploratorypatientlevelanalysesofsustainandpioneerrandomizedclinicaltrials
AT capehornmatthews impactofsemaglutideonhighsensitivitycreactiveproteinexploratorypatientlevelanalysesofsustainandpioneerrandomizedclinicaltrials
AT deremigisalessandra impactofsemaglutideonhighsensitivitycreactiveproteinexploratorypatientlevelanalysesofsustainandpioneerrandomizedclinicaltrials
AT rasmussensøren impactofsemaglutideonhighsensitivitycreactiveproteinexploratorypatientlevelanalysesofsustainandpioneerrandomizedclinicaltrials
AT weimerspetra impactofsemaglutideonhighsensitivitycreactiveproteinexploratorypatientlevelanalysesofsustainandpioneerrandomizedclinicaltrials
AT rosenstockjulio impactofsemaglutideonhighsensitivitycreactiveproteinexploratorypatientlevelanalysesofsustainandpioneerrandomizedclinicaltrials