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Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial
BACKGROUND: Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigat...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941151/ https://www.ncbi.nlm.nih.gov/pubmed/26917577 http://dx.doi.org/10.1136/thoraxjnl-2015-208035 |
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author | Hitchings, Andrew W Lai, Dilys Jones, Paul W Baker, Emma H |
author_facet | Hitchings, Andrew W Lai, Dilys Jones, Paul W Baker, Emma H |
author_sort | Hitchings, Andrew W |
collection | PubMed |
description | BACKGROUND: Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome. METHODS: This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool. RESULTS: 52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. CONCLUSION: Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. TRIAL REGISTRATION NUMBER: ISRCTN66148745 and NCT01247870. |
format | Online Article Text |
id | pubmed-4941151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49411512016-07-13 Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial Hitchings, Andrew W Lai, Dilys Jones, Paul W Baker, Emma H Thorax Chronic Obstructive Pulmonary Disease BACKGROUND: Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes. Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown. We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome. METHODS: This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations. Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo. The primary end point was mean in-hospital blood glucose concentration. Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool. RESULTS: 52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo). All were included in the primary end point analysis. The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273). No significant between-group differences were observed on any of the secondary end points. Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants. CONCLUSION: Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes. TRIAL REGISTRATION NUMBER: ISRCTN66148745 and NCT01247870. BMJ Publishing Group 2016-07 2016-02-25 /pmc/articles/PMC4941151/ /pubmed/26917577 http://dx.doi.org/10.1136/thoraxjnl-2015-208035 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Chronic Obstructive Pulmonary Disease Hitchings, Andrew W Lai, Dilys Jones, Paul W Baker, Emma H Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial |
title | Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial |
title_full | Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial |
title_fullStr | Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial |
title_full_unstemmed | Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial |
title_short | Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial |
title_sort | metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial |
topic | Chronic Obstructive Pulmonary Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941151/ https://www.ncbi.nlm.nih.gov/pubmed/26917577 http://dx.doi.org/10.1136/thoraxjnl-2015-208035 |
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