Time-action profile of inhaled insulin

Abstract

We compared the pharmacodynamics of insulin after inhalation of 99 U microcrystalline solid insulin and subcutaneous injection of 10 U regular insulin and intravenous injection of 5 U regular insulin. The time-action profiles of the three insulin administrations were studied in 11 healthy volunteers using the euglycaemic glucose clamp technique. The insulins were administered to each volunteer on three separate occasions in random order. Onset of action, assessed as glucose infusion rate, after insulin inhalation was substantially more rapid than after subcutaneous injection and half-maximal action was reached earlier (31 +/- 17 vs 54 +/- 12 min; p < 0.001). Maximal metabolic response was reached earlier after insulin inhalation in comparison to subcutaneous injection (108 +/- 49 vs 147 +/- 53 min; p < 0.001). The maximal glucose infusion rate after inhalation of insulin was lower than after subcutaneous insulin injection (6.2 +/2- 2.4 vs 9.1 +/- 2.5 mg kg-1 min-1; p < 0.001). The glucose infusion rates in the first 60 min after inhalation were significantly greater than after insulin injection (area under the glucose infusion rate curve: 0.23 +/- 0.12 vs 0.13 +/- 0.08 g kg-1 60 min-1; p < 0.001). However, the total metabolic effect after inhalation was significantly lower than after insulin injection (1.44 +/- 0.68 vs 1.90 +/- 0.47 g kg-1 360 min-1; p < 0.001). Relative effectiveness of inhaled insulin calculated with regard to the data from the intravenous insulin application was 9.5 +/- 4.1% and of the subcutaneous insulin application was 7.6 +/- 2.9%. With its rapid onset of action, inhaled insulin might have potential for clinical use.