Reliability of Dosing
Many large controlled clinical studies assessed inhaled insulin dose-to-dose variability between patients and within individual patients and found that inhaled insulin produced similar variability to that obtained with traditional insulin injections. Inaccurate dosing of insulin can cause low blood glucose, known as hypoglycemia, or high blood glucose, known as hyperglycemia. Severe hypoglycemia can cause loss of consciousness, which can result in emergency room admission. Mild to moderate forms of hypoglycemia can cause dizziness, which can be quickly treated with sugar pills or fruit juices among other things. Hyperglycemia indicates that patients are not taking enough insulin, which can be adjusted accordingly. Hyperglycemia is not immediately dangerous like hypoglycemia and is accompanied by drowsiness and loss of energy. Concerns about reliability of inhaled insulin have focused primarily on hypoglycemia.
In almost all prior published studies, blood glucose control with inhaled insulin was noninferior to injected regular insulin in both type 1 and 2 diabetes patients . The efficacy of inhaled insulin was maintained for a prolonged period of time and was preferred by patients to injected insulin and oral regimes . The similarity with injections was notable because the dosing unit with Exubera, 3 and 8 IU increments or combinations, is considerably less than the 1 IU increment typically available with pen injection insulin. Despite Exubera’s larger dosing unit, rates of hypoglycemia were lower among type 2 diabetes patients using Exubera than those using injections and declined with use over time .
In a 3-month study conducted by Novo Nordisk, the AERx inhaled insulin product candidate and insulin injections demonstrated similar rates of overall blood glucose control and hypoglycemia in type 2 diabetes patients . A 6-month study conducted by Lilly with AIR demonstrated that there were no statistical differences in efficacy or episodes of hypoglycemia among type 2 diabetes patients receiving AIR therapy or injected insulin . AIR insulin powder was available to patients in either 2 or 6 IU increments.
In summary, the previous concerns regarding inhaler dosing reliability for inhaled insulin were repeatedly addressed using a variety of inhaler systems . These studies demonstrate that insulin administration by inhalation had similar or improved repeatability to injectable insulin.