title: Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes: A Historical Matched Cohort Study.
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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ENCePP ENCEPP/SDPP/6804.
authors.affiliation: Academic Primary Care, University of Aberdeen, Aberdeen, United Kingdom.|Observational and Pragmatic Research Institute, Singapore, Singapore.
authors.forename: David B
authors.initials: DB
authors.lastname: Price
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Richard
authors.identifier: http://orcid.org/0000-0002-3890-7201
authors.initials: R
authors.lastname: Russell
authors.affiliation: Research in Real Life Ltd, Cambridge, United Kingdom.
authors.forename: Rafael
authors.identifier: http://orcid.org/0000-0001-9153-4662
authors.initials: R
authors.lastname: Mares
authors.affiliation: Cambridge Research Support, Cambridge, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Burden
authors.affiliation: Optimum Patient Care, Cambridge, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Skinner
authors.affiliation: Cambridge Research Support, Cambridge, United Kingdom.
authors.forename: Helga
authors.initials: H
authors.lastname: Mikkelsen
authors.affiliation: Observational and Pragmatic Research Institute, Singapore, Singapore.
authors.forename: Cherlyn
authors.initials: C
authors.lastname: Ding
authors.affiliation: Whitstable Medical Practice, Whitstable, Canterbury, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Brice
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Niels H
authors.initials: NH
authors.lastname: Chavannes
authors.affiliation: Department of General Practice and GRIAC Research Institute, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Janwillem W H
authors.initials: JW
authors.lastname: Kocks
authors.affiliation: Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea, United Kingdom.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Stephens
authors.affiliation: Academic Primary Care, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Haughney