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The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes

OBJECTIVE: Basal insulin glargine has a neutral effect on cardiovascular risk in type 2 diabetes (T2DM). In practice, basal insulin is often paired with a glucagon-like peptide-1 receptor agonist (GLP1-RA) or meal insulin; however, the cardiovascular implications of these combinations have not been...

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Autores principales: Retnakaran, Ravi, Pu, Jiajie, Ye, Chang, Emery, Alexandra, Kramer, Caroline K., Zinman, Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998007/
https://www.ncbi.nlm.nih.gov/pubmed/36894921
http://dx.doi.org/10.1186/s12933-023-01781-z
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author Retnakaran, Ravi
Pu, Jiajie
Ye, Chang
Emery, Alexandra
Kramer, Caroline K.
Zinman, Bernard
author_facet Retnakaran, Ravi
Pu, Jiajie
Ye, Chang
Emery, Alexandra
Kramer, Caroline K.
Zinman, Bernard
author_sort Retnakaran, Ravi
collection PubMed
description OBJECTIVE: Basal insulin glargine has a neutral effect on cardiovascular risk in type 2 diabetes (T2DM). In practice, basal insulin is often paired with a glucagon-like peptide-1 receptor agonist (GLP1-RA) or meal insulin; however, the cardiovascular implications of these combinations have not been fully elucidated. In this context, we sought to evaluate the vascular function effects of adding the GLP1-RA exenatide or meal insulin lispro to basal glargine therapy in early T2DM. METHODS: In this 20-week trial, adults with T2DM of < 7-years duration were randomized to 8-weeks treatment with (i) insulin glargine (Glar), (ii) glargine + thrice-daily lispro (Glar/Lispro), or (iii) glargine + twice-daily exenatide (Glar/Exenatide), followed by 12-weeks washout. At baseline, 8-weeks, and washout, fasting endothelial function was assessed with reactive hyperemia index (RHI) measurement by peripheral arterial tonometry. RESULTS: At baseline, there were no differences in blood pressure (BP), heart rate (HR) or RHI between participants randomized to Glar (n = 24), Glar/Lispro (n = 24), and Glar/Exenatide (n = 25). At 8-weeks, Glar/Exenatide decreased systolic BP (mean − 8.1 mmHg [95%CI − 13.9 to − 2.4], p = 0.008) and diastolic BP (mean − 5.1 mmHg [− 9.0 to − 1.3], p = 0.012) compared to baseline, with no significant changes in HR or RHI. Notably, baseline-adjusted RHI (mean ± SE) did not differ between the groups at 8-weeks (Glar 2.07 ± 0.10; Glar/Lispro 2.00 ± 0.10; Glar/Exenatide 1.81 ± 0.10; p = 0.19), nor did baseline-adjusted BP or HR. There were no differences between the groups in baseline-adjusted RHI, BP or HR after 12-weeks washout. CONCLUSION: Adding either exenatide or lispro to basal insulin therapy does not appear to affect fasting endothelial function in early T2DM. Trial Registration: ClinicalTrials.Gov NCT02194595.
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spelling pubmed-99980072023-03-10 The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes Retnakaran, Ravi Pu, Jiajie Ye, Chang Emery, Alexandra Kramer, Caroline K. Zinman, Bernard Cardiovasc Diabetol Research OBJECTIVE: Basal insulin glargine has a neutral effect on cardiovascular risk in type 2 diabetes (T2DM). In practice, basal insulin is often paired with a glucagon-like peptide-1 receptor agonist (GLP1-RA) or meal insulin; however, the cardiovascular implications of these combinations have not been fully elucidated. In this context, we sought to evaluate the vascular function effects of adding the GLP1-RA exenatide or meal insulin lispro to basal glargine therapy in early T2DM. METHODS: In this 20-week trial, adults with T2DM of < 7-years duration were randomized to 8-weeks treatment with (i) insulin glargine (Glar), (ii) glargine + thrice-daily lispro (Glar/Lispro), or (iii) glargine + twice-daily exenatide (Glar/Exenatide), followed by 12-weeks washout. At baseline, 8-weeks, and washout, fasting endothelial function was assessed with reactive hyperemia index (RHI) measurement by peripheral arterial tonometry. RESULTS: At baseline, there were no differences in blood pressure (BP), heart rate (HR) or RHI between participants randomized to Glar (n = 24), Glar/Lispro (n = 24), and Glar/Exenatide (n = 25). At 8-weeks, Glar/Exenatide decreased systolic BP (mean − 8.1 mmHg [95%CI − 13.9 to − 2.4], p = 0.008) and diastolic BP (mean − 5.1 mmHg [− 9.0 to − 1.3], p = 0.012) compared to baseline, with no significant changes in HR or RHI. Notably, baseline-adjusted RHI (mean ± SE) did not differ between the groups at 8-weeks (Glar 2.07 ± 0.10; Glar/Lispro 2.00 ± 0.10; Glar/Exenatide 1.81 ± 0.10; p = 0.19), nor did baseline-adjusted BP or HR. There were no differences between the groups in baseline-adjusted RHI, BP or HR after 12-weeks washout. CONCLUSION: Adding either exenatide or lispro to basal insulin therapy does not appear to affect fasting endothelial function in early T2DM. Trial Registration: ClinicalTrials.Gov NCT02194595. BioMed Central 2023-03-09 /pmc/articles/PMC9998007/ /pubmed/36894921 http://dx.doi.org/10.1186/s12933-023-01781-z Text en © The Author(s) 2023 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
Retnakaran, Ravi
Pu, Jiajie
Ye, Chang
Emery, Alexandra
Kramer, Caroline K.
Zinman, Bernard
The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes
title The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes
title_full The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes
title_fullStr The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes
title_full_unstemmed The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes
title_short The vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes
title_sort vascular function effects of adding exenatide or meal insulin to basal insulin therapy in early type 2 diabetes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998007/
https://www.ncbi.nlm.nih.gov/pubmed/36894921
http://dx.doi.org/10.1186/s12933-023-01781-z
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