Inhaled Technosphere insulin in comparison to subcutaneous regular human insulin: time action profile and variability in subjects with type 2 diabetes.

ABSTRACT

BACKGROUND: This study assessed time action profile and within- and between-subject variability of inhaled Technosphere Insulin (TI) compared with subcutaneous regular human insulin (sc RHI). METHODS: Thirteen subjects with type 2 diabetes (age 56 +/- 7 years, body mass index 30.4 +/- 3.0 kg.m(-2); hemoglobin A1c 6.9 +/- 0.9%; mean +/- SD) participated in this six-period crossover isoglycemic glucose clamp study. In randomized order, each subject received three single doses of TI and sc RHI on separate study days. RESULTS: Inhalation of TI resulted in a higher maximum serum insulin concentration (858 vs 438 pmol.liter(-1); p = 0.0001) and shorter intervals to maximum insulin concentration (17 vs 135 minutes; p = 0.0001) than sc RHI. Overall, 48 units of TI and 24 units of sc RHI provided comparable 3-hour insulin exposure (INS area under the curve(0-3 h) 55.8 vs 60.0 nmol.min.liter(-1), respectively). Time to maximum metabolic effect was shorter (79 vs 293 minutes; p < 0.0001), and percentage of glucose disposal during the first 3 hours was higher for TI compared with sc RHI (59 vs 27%). Within-subject variabilities of insulin exposure following inhalation of TI for 2 and 3 hours and end of study period were 19, 18, and 16% as compared with 27, 25, and 15% after sc RHI injection (p = not significant). CONCLUSION: Technosphere Insulin has a more rapid onset of action than sc RHI. About 60% of the glucose-lowering effect of TI occurs during the first 3 hours after application. In contrast, <30% of the glucose-lowering effect of sc RHI occurs in this period. Technosphere Insulin demonstrated a lower intrasubject variability during the 3-hour postprandial period, without reaching statistical significance.