Γενικός Ιατρός

Use of Inhaled Corticosteroids in Patients with Diabetes

This information is provided in response to your request for information regarding Seretide® (salmeterol
xinafoate and fluticasone propionate, (SAL/FP)).

SUMMARY

• A randomised, double-blind, crossover study compared the effects of fluticasone propionate HFA
inhalation aerosol 250 mcg 2 inhalations twice daily and montelukast 10 mg/day on glucose
control in 10 patients with type 2 diabetes mellitus and co-existing asthma or chronic obstructive
pulmonary disease (COPD). Results showed a small but statistically significant increase in percentage
glycosylated haemoglobin in those patients receiving fluticasone propionate aerosol compared to
those who received montelukast.

• A population-based cohort study revealed a 34% increased risk of developing new onset diabetes
and a 34% increase in the rate of disease progression in patients treated with inhaled corticosteroids
(ICS). This risk was directly proportional to increasing doses of inhaled corticosteroids. For patients
in the low dose ICS group (equivalent to <500 mcg per day of fluticasone propionate [FP]), there
was no significant increased risk (adjusted rate ratio [ARR] of disease progression was 1.08; 95%
CI; 0.63–1.87), compared to a 30% increase in risk for those on medium dose ICS (equivalent to
500–1000 mcg per day of FP; ARR 1.30; 95% CI 1.12–1.52) and a 54% increase risk for those on
high dose ICS (equivalent to >1000 mcg per day of FP; ARR 1.54; 95% CI 1.18–2.02).

USE OF FLUTICASONE PROPIONATE AEROSOL IN PATIENTS WITH DIABETES

A randomised, double-blind, double-dummy, crossover study compared the effects of inhaled fluticasone
propionate HFA inhalation aerosol 250 mcg, two inhalations twice daily, and montelukast 10 mg/day on
glycaemic control in adult patients with type 2 diabetes mellitus.(1) The study included 10 adult male
patients (mean age 64) with type 2 diabetes (mean glycosylated haemoglobin 6.8%) and coexisting asthma
or chronic obstructive pulmonary disease (COPD). Patients were included if their diabetes was managed
by oral hypoglycaemic medications or diet. Patients requiring insulin were excluded. The study involved
a 3 week placebo run-in period after which patients were randomised to fluticasone propionate HFA
inhalation aerosol 250 mcg, two inhalations twice daily via a spacer and a placebo tablet, or montelukast
10 mg/day and a placebo inhaler for 6 weeks. Patients were then crossed over to the opposite treatment
arm for an additional 6 weeks with no washout period between treatment arms. Percentage of glycosylated
haemoglobin (% HbA1c) was measured before and after each treatment arm.
Results showed that fluticasone propionate aerosol was associated with an average increase of glycosylated
haemoglobin of 0.11% ± 0.17% while montelukast was associated with an average reduction of 0.14% ±
0.26%. The difference between treatments in this measure was statistically significant (mean difference of
FP minus montelukast = 0.25%; P<0.025). However, this difference did not meet the threshold for what is
generally considered a clinically relevant change (0.5%).

DIABETES ONSET AND PROGRESSION OF DISEASE IN PATIENTS RECEIVING INHALED
CORTICOSTEROIDS

Suissa et al conducted a population-based cohort study to determine if there was an increased risk of new
onset diabetes, or if there was a progression of type 2 diabetes requiring insulin therapy, in patients treated
with inhaled corticosteroids.(2) All doses of inhaled corticosteroids (which included beclomethasone,

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budesonide, triamcinolone, fluticasone, and flunisolide) that were dispensed prior to the index date were
converted to fluticasone propionate equivalents, and categorised as high (≥ fluticasone propionate 1000
mcg/day), moderate (500–999 mcg/day), or low (< 500 mcg/day). The number of patients on each drug
was not reported. Ten controls were matched for each case.
After adjusting for differences in co-variates, results showed that current use of inhaled corticosteroids
was associated with a 34% increased risk of developing diabetes. Disease progression, as defined by a
first prescription of insulin among oral-hypoglycaemic agent patients, also increased by 34% in patients
treated with inhaled corticosteroids. These increases were directly proportional to increased inhaled
corticosteroid dose, and were greatest in patients receiving the equivalent of ≥ 1000 mcg/day of fluticasone
propionate. For patients in the low dose ICS group, there was no significant increased risk (adjusted
rate ratio of disease progression was 1.08; 95% CI; 0.63–1.87), compared to a 30% increase in risk
for those on medium dose ICS (1.30; 95% CI 1.12–1.52) and a 54% increase risk for those on high
dose ICS (1.54; 95% CI 1.18–2.02).
Some information contained in this response may not be included in the approved Summary of
Product Characteristics. This response is not intended to offer recommendations for administering
this product in a manner inconsistent with its approved labelling.
Adverse events should be reported. Reporting forms and information can be found at
www.mhra.gov.uk/yellowcard. Adverse events should also be reported to GlaxoSmithKline on
0800 221 441.

If you become aware of patients who have received this product at any time during their pregnancy,
we encourage healthcare professionals to report such information to the company.
This response was developed according to the principles of evidence-based medicine and therefore
references may not be all-inclusive.

REFERENCE(S)

1. Faul JL, Wilson SR, Chu JW, et al. The effect of inhaled corticosteroid on glucose control in type 2
diabetes. Clin Med Res 2009;7:14–20.*
2. Suissa S, Kezouh A, Ernst P. Inhaled corticosteroids and the risks of diabetes onset and progression.
Am J Med 2010 123;1001–1006.*
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