ICS use in COPD tied to increased T2DM onset

Patients with chronic obstructive pulmonary disease (COPD) who initiate treatment with inhaled corticosteroids (ICS) may have an elevated risk of developing type 2 diabetes mellitus (T2DM), according to a matched cohort study.

“The results of this large historical cohort study indicate that ICS initiation as the first maintenance treatment for patients with COPD is associated with greater risk of developing T2DM as compared with [long-acting bronchodilator (LABD)] treatment,” said the study authors led by Professor David Price from the Observational and Pragmatic Research Institute, Singapore.

Additionally, a mean daily dose of ≥500 μg of a fluticasone propionate-equivalent was associated with elevated risks of T2DM onset and progression and onset of osteoporosis compared with a mean dose of <250 μg/day, they said.

The study authors pulled data from two UK databases* and identified 37,922 patients aged ≥40 years without asthma who initiated use of ICS or LABDs for COPD between 1990 and 2015. Outcomes assessed were the association of ICS treatment in COPD with onset (n=17,970; mean age 68 years, 59 percent male) or accelerated progression of T2DM (n=804; mean age 71 years, 66 percent male), or onset of osteoporosis (n=19,898; mean age 68 years, 62 percent male). Patients needed to have <5 prescriptions of oral corticosteroids per study year. Only outcomes beginning 1.5 years after LABD or ICS initiation were assessed.  

Over a median follow-up period of 3.7–5.6 years, the risk of diabetes onset was elevated among patients who initiated ICS compared with LABDs (adjusted hazard ratio [adjHR], 1.27, 95 percent confidence interval [CI], 1.07–1.50; p=0.006). [NPJ Prim Care Respir Med 2019;29:38]

While there was no apparent increase in the overall risk of diabetes progression (adjHR, 1.04, 95 percent CI, 0.87–1.25; p=0.67) and a non-significant increase in osteoporosis onset (adjHR, 1.13, 95 percent CI, 0.93–1.39; p=0.22) with ICS vs LABD treatment initiation, a mean ICS exposure of ≥500 μg/day was tied to a higher risk of all three outcomes compared with a <250 μg/day dose of a fluticasone propionate equivalent.

There was no increased risk of any of the three outcomes with cumulative ICS exposure. The authors theorized that the mean daily exposure could be more reflective of treatment intensity leading to the outcomes in this study, in contrast to cumulative exposure which could be the result of low doses of ICS over a long-term period. 

“[T]he benefits of ICS for patients with COPD, particularly those with milder disease (GOLD** A/B), and particularly in comparison with LABDs, remain in question,” said the authors.

According to the current GOLD strategy, ICS initiation is recommended in patients with a history of hospitalization for COPD-related exacerbations, those who frequently experience exacerbations and symptoms despite optimal treatment with LABDs, and those with a blood eosinophil count of ≥300 cells/μL. [Global Strategy for the Diagnosis, Management, and Prevention of COPD 2020 Report, https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.1wms.pdf, accessed 3 December 2019]

“[T]here was considerable use of ICS outside of current GOLD recommendations [in this study], with over half of patients in 2011 GOLD groups A/B prescribed ICS,” they noted.

“Our findings support the importance of careful selection of COPD therapies and prescribing ICS only when indicated and at the lowest possible doses. Moreover, these findings support current GOLD recommendations for prescribing ICS selectively to patients with frequent COPD exacerbations despite optimal bronchodilator therapy,” the authors concluded.