Absorption and metabolic effect of inhaled insulin: intrapatient variability after inhalation via the Aerodose insulin inhaler in patients with type 2 diabetes.

OBJECTIVE To compare the intrapatient variability of the pharmacokinetic and pharmacodynamic responses to inhaled regular insulin (INH) delivered via the Aerodose Insulin Inhaler with that of subcutaneously injected regular insulin (SC) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 15 patients with type 2 diabetes (nonsmokers, 10 men, aged 47-77 years) received two 240-unit doses of INH, delivered via a clinical Aerodose Insulin Inhaler and two 24-unit doses of SC under euglycemic clamp conditions on four separate study days. Glucose infusion rates (GIRs) and serum insulin concentrations were monitored over the following 8 h. Comparisons of intrapatient coefficients of variation (CV) were used to assess the reproducibility of INH versus SC. RESULTS INH showed a bioavailability (0-8 h postdosing) of 16% and biopotency of 13% relative to SC. Comparison of the CVs (%) for area under the curve for serum insulin and GIR between INH and SC showed no significant differences between the treatments during 0-3 h (19% for INH versus 23% for SC) or 0-8 h (22% for INH versus 16% for SC). INH exhibited a shorter time to peak insulin concentration (T(max) [mean +/- SD] 76 +/- 51 vs. 193 +/- 66 min) and shorter time to peak metabolic effect (T(GIRmax) 170 +/- 53 vs. 244 +/- 75 min) compared with SC (P < 0.001). No adverse events were observed. CONCLUSIONS Comparable dosing reproducibility and shorter time to peak action of INH compared with SC suggest that INH delivered via the Aerodose Insulin Inhaler can provide reliable preprandial dosing of insulin in patients with type 2 diabetes.