The introduction of inhaled insulin as a therapeutic option for patients with diabetes type 1 or type 2 offers the more than 5 million diabetic Americans who require insulin a less painful and more convenient alternative to standard insulin injections. Inhaled insulin (Exubera Inhalation Powder) received FDA approval for the treatment of adults with diabetes in January 2006.

Patients with type 1 diabetes can add inhaled insulin to longer-acting insulins to replace the short-acting insulin they must take with meals. Patients with type 2 diabetes can use it either alone or in combination with oral antidiabetic medications or longer acting insulins.

The new inhaled insulin contains a fine, dry-powder insulin that is stable at room temperature, dispersible, and is easily turned back into a liquid. As a result, the particles penetrate the gas-blood barrier in the lung and enter the bloodstream more quickly than subcutaneously injected insulin.

Inhaled insulin has the added benefit of convenience, which may help enhance patient adherence to treatment.

The Evidence
To date, about 25,000 adults with type 1 or type 2 diabetes have used Exubera in clinical trials.

In clinical trials, inhaled insulin reached peak serum insulin levels at an average of 49 minutes compared with 105 minutes for injected insulin, but its duration of action was similar to or longer than that of injected insulin (Diabetes Care. 2005; 28:2400-2405).

A 6-month randomized trial of 300 patients with type 2 diabetes showed that inhaled insulin was as effective as injected insulin in lowering HbA_1clevels (Diabetes Care. 2004; 27:2356-2362). Inhaled insulin also allowed more patients to reach the target HbA_1c <7.0% goal compared with injections (46.9% versus 31.7%, respectively). More patients assigned to inhaled insulin reported being satisfied with the treatment than those assigned to injections.

In another study involving 309 patients with type 2 diabetes and HbA_1c levels of 8% to 11%, Exubera improved glycemic control when used instead of or in addition to oral combination therapy (Ann Intern Med. 2005; 143:549-558). After 12 weeks of therapy, adding inhaled insulin to oral therapy increased the proportion of those reaching the target HbA_1c level of <7% by 32% compared with oral therapy alone.

Side Effects, Contraindications
Reported side effects of inhaled insulin include hypoglycemia, hyperglycemia, serious allergic reactions, cough, dry mouth, and chest discomfort. Perhaps the most worrisome adverse event is a reduction in lung function. In clinical trials, only minor pulmonary changes were seen early in the therapy, and those were not progressive. However, physicians should test patients for pulmonary function, such as by spirometry, after starting therapy, then 6 months later, and then annually, to monitor pulmonary function.

Early data suggest that the drug can be safely taken for up to 4 years by patients with normal lung function.

Exubera is contraindicated in the following patient populations:
• Those who smoke or stopped smoking less than 6 months ago
• Patients with unstable or poorly controlled lung disease, such as asthma, chronic obstructive pulmonary disease, or emphysema
• Anyone allergic to insulin or any of its active ingredients
• Children or adolescents <18 years of age

The FDA has developed a 15-page medication guide for patients (available online at www.fda.gov/cder/foi/label/2006/021868mg.pdf) that explains who should not use this product. Pharmacists must give the guide to any patient filling a prescription for inhaled insulin.

How to Use Inhaled Insulin
Exubera is available in 1- and 3-mg blister packets. The entire packet is loaded into the inhaler. When Exubera is used as mealtime insulin, it should be inhaled within 10 minutes before the meal.