OBJECTIVE -This study compares the time-action profile of inhaled insulin (INH; Exubera) with that of subcutaneously injected insulin lispro (ILP) or regular human insulin (RHI) in healthy volunteers.
RESEARCH DESIGN AND METHODS-In this open-label, randomized, three-way, crossover study, 17 healthy male volunteers were given each of the following treatments in random order: INH (6 mg), ILP (18 units), or RHI (18 units). Glucose infusion rates and serum insulin concentrations were monitored over 10 h. CONCLUSIONS -INH had a faster onset of action than RHI or ILP and a duration of action longer than ILP and comparable to RHI. These characteristics suggest that inhaled insulin is suitable for prandial insulin supplementation in patients with diabetes.
RESULTS
Diabetes Care 28:1077-1082, 2005T he pulmonary delivery of insulin is currently being studied as an alternative method of insulin administration. Early studies have shown promising results, and it has been demonstrated that the onset of action of inhaled insulin is faster than that of regular human insulin (RHI), resembling that of rapid-acting insulin analogs (1-5). RHI has several disadvantages when its use for controlling prandial glycemia is considered. A relatively slow onset of action and a prolonged duration of action results in a suboptimal time-action profile (6). In addition, subcutaneous insulin injections are often considered inconvenient and cause anxiety for many patients (7).Inhaled insulin may be a viable alternative to prandial insulin administration for patients with diabetes because of its more favorable pharmacokinetic profile and less invasive route of administration. However, a direct comparison of the pharmacodynamic properties of INH and subcutaneously injected rapid-acting insulin analogs has not yet been performed. The purpose of this study was to compare the pharmacokinetic and pharmacodynamic properties of human insulin administered to the lung using a novel drypowder inhaled insulin delivery system with those of subcutaneously injected RHI and the rapid-acting insulin analog insulin lispro (ILP).
RESEARCH DESIGN ANDMETHODS -Eighteen healthy, nonsmoking male volunteers (age 28 Ϯ 4 years, BMI 23.6 Ϯ 2.0 kg/m 2 ) participated in this open-label, randomized, three-way, crossover study. Seventeen participants completed the study; one withdrew after receiving his first study treatment (INH) due to an adverse event (sepsis) attributed to the testing procedure and not the study treatment.Subjects gave written informed consent and underwent a physical examinat i o n , 1 2 -l e a d e l e c t r o c a r d i o g r a m recording, and clinical laboratory tests. All subjects had normal lung function (mean forced expiratory volume in 1 s [FEV 1 ] Ͼ80% of predicted normal value; FEV 1 -to-forced vital capacity ratio Ͼ0.80) as measured in a standing position using a Spirovit Baar, Switzerland). Nonsmoking status was verified using a negative urine cotinine excretion test (LCMS method, API 3ϩ; Perkin-Elmer, Weiterstadt, Ger-