The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma

Abstract

Aim: To investigate the effect of prior administration of a bronchodilator on the absorption of inhaled insulin in people with asthma treated with inhaled corticosteroids.

Methods: A single-centre, randomized, open-label, two-period cross-over trial was carried out in 41 nondiabetic subjects with asthma treated with inhaled steroids, with reversible bronchoconstriction (Rev+; n= 25) or without reversible bronchoconstriction (Rev-; n= 16). A dose of 0.10 U kg(-1) inhaled human insulin was administered on each dosing day with or without prior administration of the bronchodilator terbutaline (in random order).

Results: Prior administration of terbutaline led to a 44% increase in absorption of insulin over 6 h for the Rev+ group compared with no prior administration of bronchodilator [ratio (95% confidence interval) 1.44 (1.13, 1.82), P= 0.004], whereas no effect was seen for the Rev- or the whole group. The maximum insulin concentration (C(max)) increased by 34% for the Rev+ group (P = 0.018) and 17% for the whole group (P= 0.046), whereas no significant effect of prior terbutaline administration was seen for Rev-. The time to C(max) was not significantly different for the Rev+ group, whereas it was approximately 30% longer after bronchodilator administration for the Rev- group (P= 0.044) and the whole group (P= 0.032).

Conclusions: In people with asthma and reversible bronchoconstriction, the administration of a bronchodilator prior to administration of inhaled insulin led to increased absorption of insulin, whereas no effect on insulin absorption in subjects without significant reversibility could be detected.

Figure 1

Mean serum insulin concentration curves. (a) All subjects. (b) Rev− subgroup [subjects with forced expiratory volume in 1 s (FEV₁) increase <12% at baseline]. (c) Rev+ subgroup (subjects with FEV₁ increase ≥12% at baseline). Solid line, inhaled insulin with no prior administration of bronchodilator; dotted line, inhaled insulin with administration of bronchodilator 30 min before inhalation of insulin

Figure 2

Mean plasma glucose concentration curves. (a) All subjects. (b) Rev− subgroup [subjects with forced expiratory volume in 1 s (FEV₁) increase <12% at baseline]. (c) Rev+ subgroup (subjects with FEV₁ increase ≥12% at baseline). Solid line, inhaled insulin with no prior administration of bronchodilator; dotted line, inhaled insulin with administration of bronchodilator 30 min before inhalation of insulin