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

doi:10.1371/journal.pone.0162903

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

PLoS One. 2016 Sep 22;11(9):e0162903. doi: 10.1371/journal.pone.0162903. eCollection 2016.

Authors

David B Price^{1

2}, Richard Russell³, Rafael Mares⁴, Anne Burden⁵, Derek Skinner⁶, Helga Mikkelsen⁵, Cherlyn Ding², Richard Brice⁷, Niels H Chavannes⁸, Janwillem W H Kocks⁹, Jeffrey W Stephens¹⁰, John Haughney¹

Affiliations

¹ Academic Primary Care, University of Aberdeen, Aberdeen, United Kingdom.
² Observational and Pragmatic Research Institute, Singapore, Singapore.
³ Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
⁴ Research in Real Life Ltd, Cambridge, United Kingdom.
⁵ Cambridge Research Support, Cambridge, United Kingdom.
⁶ Optimum Patient Care, Cambridge, United Kingdom.
⁷ Whitstable Medical Practice, Whitstable, Canterbury, United Kingdom.
⁸ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
⁹ Department of General Practice and GRIAC Research Institute, University Medical Center Groningen, Groningen, the Netherlands.
¹⁰ Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea, United Kingdom.

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.

Grants and 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.