There are an estimated 16 million diabetics in the United States today. This number can be further subdivided into Type 1 (juvenile-onset) or Type 2 (adult-onset) diabetics. At the root of both types of diabetes is the inability to control levels of blood glucose, the main energy source for the human body. This is due to either a deficiency or developed insensitivity to insulin which mediates the uptake of glucose from the bloodstream into the cells.
There are many long term complications including stroke, heart disease, kidney disease, blindness, and loss of sensation in the limbs all due to an excess of glucose in the blood.
Fortunately, insulin therapy can delay the onset and slow the progress of complications of diabetes by as much as 35-60%. Insulin therapy currently involves either oral medications or subcutaneous self-injections. Injections are required for Type 1 diabetics and if oral medications fail in Type 2 diabetics.
Nevertheless, these injections can obviously be undesirable due to local discomfort and disruption of normal lifestyle. As a result, there has been constant research into alternative forms of insulin delivery. Recently, inhaled insulin has been gaining ground as a potential therapy. The pulmonary system with its extensive blood supply and easy access to the outside world would seem like an excellent candidate for drug administration. However, there have been many problems surrounding this form of delivery. Blood glucose must ideally be maintained throughout the day in the range of 64-112 mg/dL. This requires that a measured amount of insulin be administered on a time schedule centered around meals to provide adequate control. There must be consistency in the amount of insulin delivered and received by the body with each dosing.
The pulmonary system of people does not always exhibit this consistency due to the anatomical differences between individuals as well as differences in breathing patterns. One study in 1993 utilizing an aerosolized insulin preparation demonstrated this variability with a 43-71% decrease in glucose levels among 6 patients. Furthermore, the effect of inhaled insulin is rapid, but is not maintained.
In the same study of 1993, insulin absorption quickly peaked near 40 minutes while subcutaneous injections have a slow peak at 144 minutes. This slow peak and fall helps to maintain glucose levels appropriately whereas the fast peak and fall can initially send the patient into dangerously low levels of blood sugar and subsequently high levels before the next dose.
But that was in 1993 and aside from the Y2K bug, we have much to look forward to. Inhale Therapeutics System in partnership with Pfizer has created a novel form of pulmonary insulin and delivery system which has been demonstrated to have dose to dose consistency similar to injectable insulin with respect to the amount of insulin absorbed. The new portable aerosol delivery system is about the size of a flashlight and it converts a packet of fine insulin powder into an aerosol. The packaged powder is stable under a great range of environments including room temperature. One or two inhalations provides a therapeutic dose and it is mechanically operated without requiring an external power source.
Two studies were conducted comparing subcutaneous insulin versus inhaled insulin with measurements of HbA1c which is a measure of glucose control over the prior 2-3 months. The first study of 70 type 1 diabetics showed a decrease in Hb1Ac from 8.5% to 7.7% over 3 months in the injection group whereas the inhaled group averaged a decrease from 8.5% to 7.8%. In the second study of 50 patients with type 2 diabetes, the drop in Hb1AC over 3 months was virtually identical. The incidence of undesirably low blood glucose was similar in both the injection and inhalant groups, no changes were noted in the pulmonary function of subjects, and it was well tolerated.
Moreover, 80% of the type 1 participants and 92% of the type 2 participants who received inhaled insulin, opted to continue on the inhaled preparation. Nevertheless, patients were still required to take an injection at night before bedtime in order to maintain blood glucose levels throughout the night. Currently, inhaled insulin is in its last phase of testing before FDA submission and potential approval. If approved, it may provide a less painful means of controlling diabetes and preventing the dangerous outcomes for all diabetic patients.