Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes: A Historical Matched Cohort Study

David B. Price, Richard Russell, Rafael Mares, Anne Burden, Derek Skinner, Helga Mikkelsen, Cherlyn Ding, Richard Brice, Niels H. Chavannes, Janwillem W. H. Kocks, Jeffrey W. Stephens, John Haughney

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Abstract

BACKGROUND: Management guidelines for chronic obstructive pulmonary disease (COPD) recommend that inhaled corticosteroids (ICS) are prescribed to patients with the most severe symptoms. However, these guidelines have not been widely implemented by physicians, leading to widespread use of ICS in patients with mild-to-moderate COPD. Of particular concern is the potential risk of worsening diabetic control associated with ICS use. 

Here we investigate whether ICS therapy in patients with COPD and comorbid type 2 diabetes mellitus (T2DM) has a negative impact on diabetic control, and whether these negative effects are dose-dependent.

METHODS AND FINDINGS: This was a historical matched cohort study utilising primary care medical record data from two large UK databases. We selected patients aged ≥40 years with COPD and T2DM, prescribed ICS (n = 1360) or non-ICS therapy (n = 2642) between 2008 and 2012. The primary endpoint was change in HbA1c between the baseline and outcome periods. After 1:1 matching, each cohort consisted of 682 patients. Over the 12-18-month outcome period, patients prescribed ICS had significantly greater increases in HbA1c values compared with those prescribed non-ICS therapies; adjusted difference 0.16% (95% confidence interval [CI]: 0.05-0.27%) in all COPD patients, and 0.25% (95% CI: 0.10-0.40%) in mild-to-moderate COPD patients. Patients in the ICS cohort also had significantly more diabetes-related general practice visits per year and received more frequent glucose strip prescriptions, compared with those prescribed non-ICS therapies. Patients prescribed higher cumulative doses of ICS (>250 mg) had greater odds of increased HbA1c and/or receiving additional antidiabetic medication, and increased odds of being above the Quality and Outcomes Framework (QOF) target for HbA1c levels, compared with those prescribed lower cumulative doses (≤125 mg).

CONCLUSION: For patients with COPD and comorbid T2DM, ICS therapy may have a negative impact on diabetes control. Patients prescribed higher cumulative doses of ICS may be at greater risk of diabetes progression.

TRIAL REGISTRATION: ENCePP ENCEPP/SDPP/6804.

Original languageEnglish
Article numbere0162903
Pages (from-to)1-17
Number of pages17
JournalPloS ONE
Volume11
Issue number9
DOIs
Publication statusPublished - 22 Sep 2016

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Pulmonary diseases
adrenal cortex hormones
Medical problems
cohort studies
noninsulin-dependent diabetes mellitus
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
Type 2 Diabetes Mellitus
Adrenal Cortex Hormones
Cohort Studies
glycohemoglobin
therapeutics
diabetes
dosage
confidence interval
Guidelines
Confidence Intervals
hypoglycemic agents
Therapeutics
endpoints

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Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes : A Historical Matched Cohort Study. / Price, David B.; Russell, Richard; Mares, Rafael; Burden, Anne; Skinner, Derek; Mikkelsen, Helga; Ding, Cherlyn; Brice, Richard; Chavannes, Niels H.; Kocks, Janwillem W. H.; Stephens, Jeffrey W.; Haughney, John.

In: PloS ONE, Vol. 11, No. 9, e0162903, 22.09.2016, p. 1-17.

Research output: Contribution to journalArticle

Price, DB, Russell, R, Mares, R, Burden, A, Skinner, D, Mikkelsen, H, Ding, C, Brice, R, Chavannes, NH, Kocks, JWH, Stephens, JW & Haughney, J 2016, 'Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes: A Historical Matched Cohort Study', PloS ONE, vol. 11, no. 9, e0162903, pp. 1-17. https://doi.org/10.1371/journal.pone.0162903
Price, David B. ; Russell, Richard ; Mares, Rafael ; Burden, Anne ; Skinner, Derek ; Mikkelsen, Helga ; Ding, Cherlyn ; Brice, Richard ; Chavannes, Niels H. ; Kocks, Janwillem W. H. ; Stephens, Jeffrey W. ; Haughney, John. / Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes : A Historical Matched Cohort Study. In: PloS ONE. 2016 ; Vol. 11, No. 9. pp. 1-17.
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abstract = "BACKGROUND: Management guidelines for chronic obstructive pulmonary disease (COPD) recommend that inhaled corticosteroids (ICS) are prescribed to patients with the most severe symptoms. However, these guidelines have not been widely implemented by physicians, leading to widespread use of ICS in patients with mild-to-moderate COPD. Of particular concern is the potential risk of worsening diabetic control associated with ICS use. Here we investigate whether ICS therapy in patients with COPD and comorbid type 2 diabetes mellitus (T2DM) has a negative impact on diabetic control, and whether these negative effects are dose-dependent.METHODS AND FINDINGS: This was a historical matched cohort study utilising primary care medical record data from two large UK databases. We selected patients aged ≥40 years with COPD and T2DM, prescribed ICS (n = 1360) or non-ICS therapy (n = 2642) between 2008 and 2012. The primary endpoint was change in HbA1c between the baseline and outcome periods. After 1:1 matching, each cohort consisted of 682 patients. Over the 12-18-month outcome period, patients prescribed ICS had significantly greater increases in HbA1c values compared with those prescribed non-ICS therapies; adjusted difference 0.16{\%} (95{\%} confidence interval [CI]: 0.05-0.27{\%}) in all COPD patients, and 0.25{\%} (95{\%} CI: 0.10-0.40{\%}) in mild-to-moderate COPD patients. Patients in the ICS cohort also had significantly more diabetes-related general practice visits per year and received more frequent glucose strip prescriptions, compared with those prescribed non-ICS therapies. Patients prescribed higher cumulative doses of ICS (>250 mg) had greater odds of increased HbA1c and/or receiving additional antidiabetic medication, and increased odds of being above the Quality and Outcomes Framework (QOF) target for HbA1c levels, compared with those prescribed lower cumulative doses (≤125 mg).CONCLUSION: For patients with COPD and comorbid T2DM, ICS therapy may have a negative impact on diabetes control. Patients prescribed higher cumulative doses of ICS may be at greater risk of diabetes progression.TRIAL REGISTRATION: ENCePP ENCEPP/SDPP/6804.",
author = "Price, {David B.} and Richard Russell and Rafael Mares and Anne Burden and Derek Skinner and Helga Mikkelsen and Cherlyn Ding and Richard Brice and Chavannes, {Niels H.} and Kocks, {Janwillem W. H.} and Stephens, {Jeffrey W.} and John Haughney",
note = "Funding: The analyses were funded by Boehringer Ingelheim. Access to data from the Optimum Patient Care Research Database was co-funded by Research in Real Life Ltd. The funder, Boehringer Ingelheim, had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Rafael Mares is employed by Research in Real Life Ltd., which provided support in the form of salary for author RM but did not have any additional role in the study design, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section. Acknowledgments The authors wish to thank Vicky Thomas, Elizabeth Gardener, Rosie McDonald, Simon Yau and J.B. Soriano for critical reading of the manuscript. Our thanks also go to other colleagues at Research in Real Life Ltd. for valuable discussions.",
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TY - JOUR

T1 - Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes

T2 - A Historical Matched Cohort Study

AU - Price, David B.

AU - Russell, Richard

AU - Mares, Rafael

AU - Burden, Anne

AU - Skinner, Derek

AU - Mikkelsen, Helga

AU - Ding, Cherlyn

AU - Brice, Richard

AU - Chavannes, Niels H.

AU - Kocks, Janwillem W. H.

AU - Stephens, Jeffrey W.

AU - Haughney, John

N1 - Funding: The analyses were funded by Boehringer Ingelheim. Access to data from the Optimum Patient Care Research Database was co-funded by Research in Real Life Ltd. The funder, Boehringer Ingelheim, had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Rafael Mares is employed by Research in Real Life Ltd., which provided support in the form of salary for author RM but did not have any additional role in the study design, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section. Acknowledgments The authors wish to thank Vicky Thomas, Elizabeth Gardener, Rosie McDonald, Simon Yau and J.B. Soriano for critical reading of the manuscript. Our thanks also go to other colleagues at Research in Real Life Ltd. for valuable discussions.

PY - 2016/9/22

Y1 - 2016/9/22

N2 - BACKGROUND: Management guidelines for chronic obstructive pulmonary disease (COPD) recommend that inhaled corticosteroids (ICS) are prescribed to patients with the most severe symptoms. However, these guidelines have not been widely implemented by physicians, leading to widespread use of ICS in patients with mild-to-moderate COPD. Of particular concern is the potential risk of worsening diabetic control associated with ICS use. Here we investigate whether ICS therapy in patients with COPD and comorbid type 2 diabetes mellitus (T2DM) has a negative impact on diabetic control, and whether these negative effects are dose-dependent.METHODS AND FINDINGS: This was a historical matched cohort study utilising primary care medical record data from two large UK databases. We selected patients aged ≥40 years with COPD and T2DM, prescribed ICS (n = 1360) or non-ICS therapy (n = 2642) between 2008 and 2012. The primary endpoint was change in HbA1c between the baseline and outcome periods. After 1:1 matching, each cohort consisted of 682 patients. Over the 12-18-month outcome period, patients prescribed ICS had significantly greater increases in HbA1c values compared with those prescribed non-ICS therapies; adjusted difference 0.16% (95% confidence interval [CI]: 0.05-0.27%) in all COPD patients, and 0.25% (95% CI: 0.10-0.40%) in mild-to-moderate COPD patients. Patients in the ICS cohort also had significantly more diabetes-related general practice visits per year and received more frequent glucose strip prescriptions, compared with those prescribed non-ICS therapies. Patients prescribed higher cumulative doses of ICS (>250 mg) had greater odds of increased HbA1c and/or receiving additional antidiabetic medication, and increased odds of being above the Quality and Outcomes Framework (QOF) target for HbA1c levels, compared with those prescribed lower cumulative doses (≤125 mg).CONCLUSION: For patients with COPD and comorbid T2DM, ICS therapy may have a negative impact on diabetes control. Patients prescribed higher cumulative doses of ICS may be at greater risk of diabetes progression.TRIAL REGISTRATION: ENCePP ENCEPP/SDPP/6804.

AB - BACKGROUND: Management guidelines for chronic obstructive pulmonary disease (COPD) recommend that inhaled corticosteroids (ICS) are prescribed to patients with the most severe symptoms. However, these guidelines have not been widely implemented by physicians, leading to widespread use of ICS in patients with mild-to-moderate COPD. Of particular concern is the potential risk of worsening diabetic control associated with ICS use. Here we investigate whether ICS therapy in patients with COPD and comorbid type 2 diabetes mellitus (T2DM) has a negative impact on diabetic control, and whether these negative effects are dose-dependent.METHODS AND FINDINGS: This was a historical matched cohort study utilising primary care medical record data from two large UK databases. We selected patients aged ≥40 years with COPD and T2DM, prescribed ICS (n = 1360) or non-ICS therapy (n = 2642) between 2008 and 2012. The primary endpoint was change in HbA1c between the baseline and outcome periods. After 1:1 matching, each cohort consisted of 682 patients. Over the 12-18-month outcome period, patients prescribed ICS had significantly greater increases in HbA1c values compared with those prescribed non-ICS therapies; adjusted difference 0.16% (95% confidence interval [CI]: 0.05-0.27%) in all COPD patients, and 0.25% (95% CI: 0.10-0.40%) in mild-to-moderate COPD patients. Patients in the ICS cohort also had significantly more diabetes-related general practice visits per year and received more frequent glucose strip prescriptions, compared with those prescribed non-ICS therapies. Patients prescribed higher cumulative doses of ICS (>250 mg) had greater odds of increased HbA1c and/or receiving additional antidiabetic medication, and increased odds of being above the Quality and Outcomes Framework (QOF) target for HbA1c levels, compared with those prescribed lower cumulative doses (≤125 mg).CONCLUSION: For patients with COPD and comorbid T2DM, ICS therapy may have a negative impact on diabetes control. Patients prescribed higher cumulative doses of ICS may be at greater risk of diabetes progression.TRIAL REGISTRATION: ENCePP ENCEPP/SDPP/6804.

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DO - 10.1371/journal.pone.0162903

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JF - PloS ONE

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