The approval of inhaled insulin makes it the first new method of delivery other than injection since insulin was first discovered nearly a century ago. The introduction of inhaled insulin as a therapeutic option offers the more than 5 million Americans with diabetes who require insulin a less painful and more convenient alternative to standard insulin injections.
Exubera (insulin human [rDNA origin]) Inhalation Powder (Pfizer) was approved by the FDA on January 27, 2006, for the treatment of adults with type 1 or 2 diabetes. 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 and/or longer-acting insulins.
"Exubera represents another new option for therapy that will be able to be used to help more people with diabetes achieve the recommended goal of blood glucose that we know can dramatically reduce the risk for complications," said Lawrence Blonde, MD, FACP, director of the Diabetes Clinical Research Unit at the Ochsner Clinic Foundation, New Orleans, La.
Pulmonary Delivery of Insulin
Various needleless insulin delivery formulations have been explored throughout the years.
The development of pulmonary delivery systems for insulin began in 1925. But early efforts were stymied by studies showing that most of the insulin that was sprayed or inhaled through the mouth ended up being deposited on the pharynx.
Exubera 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 injected insulin.
In a clinical trial comparing inhaled insulin and subcutaneously injected rapid-acting insulin, both treatments reached peak serum insulin levels at an average of 45 minutes. However, the duration of action with the inhaled form was longer than that of subcutaneous insulin (480 vs 360 min) (Diabetes Care. 2005;28:2400-2405).
Inhaled insulin has the potential to enhance acceptability of insulin treatment. Dr Blonde described a survey study of 779 men and women with type 2 diabetes from 7 different countries, all of whom had a hemoglobin (Hb) A1c >8% with their current therapy (Diabetes Care. 2005; 28: 427-428). "Patients with un?controlled type 2 diabetes who were given the hypothetical option of Exubera were 3 times more likely to choose an insulin regimen than those who were only given the option of currently available therapy, and inhaled insulin was the most frequently chosen treatment," says Dr Blonde.
Clinical Trial Experience
To date, about 2500 adults with type 1 or type 2 diabetes have used Exubera in clinical trials.
A 6-month randomized trial of 300 patients with type 2 diabetes found that inhaled insulin was as effective as injected insulin in lowering HbA1c levels (Diabetes Care. 2004;27:2356-2362). Inhaled insulin also allowed more pa?tients to achieve the target HbA1c goal of <7.0% (46.9% vs 31.7%). In addition more patients assigned to inhaled insulin reported being satisfied with the treatment (P <.001).
In another study involving 309 pa?tients with type 2 diabetes and HbA1c levels of 8% to 11%, Exubera was shown to improve 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 allowed 32% of patients to achieve the target HbA1c level of <7% compared with oral therapy alone (Table).
Safety of Inhaled Insulin
All insulin treatments can be associated with hypoglycemia and rare but potentially serious allergic reactions. Cough was more frequent with Exubera than injectable insulin in clinical trials. Cough was mostly mild and decreased with continued use.
The Exubera trials were the first to specifically study lung function in people with diabetes. "We know that in the trials to date there were very minor pulmonary changes that occurred early and were not progressive and were very small (about 1% of baseline)," observes Dr Blonde. He added that the average person experiences about a 1% variation in pulmonary function on any given day, and that variation does not affect daily activities. Data to date indicate that the drug can be safely taken by individuals with normal lung function for up to 4 years (Poster presented at the American Diabetes Association 64th An?nual Ses?sions; June 5-8, 2004, Or?lando, Fla).
All patients will be recommended to have pulmonary function (ie, spirometry) testing before initiating Exubera therapy, then after the first 6 months of use, and annually thereafter, even those without pulmonary symptoms.
Important Patient Information
The FDA has developed a 15-page medication guide (available at www.fda.gov/cder/foi/label/2006/021868mg.pdf) that is designed especially for patients. Pharmacists must give the guide to any patient filling a prescription for inhaled insulin. The guide includes the following caveats for patients:
? Do not use Exubera if you smoke or stopped smoking <6 months ago; stop using Exubera if you start smoking or resume smoking
? Do not use Exubera if you have unstable or poorly controlled lung disease (ie, poorly controlled asthma, chronic obstructive pulmonary disease, or emphysema)
? Do not use Exubera if you are allergic to insulin or any of its active ingredients
? Exubera should not be used by children or adolescents <18 years of age
? Before taking Exubera, tell your physician if you have lung disease or breathing problems, are using inhaled medications, have liver or kidney problems, are pregnant or plan to become pregnant, are breast-feeding or plan to breast-feed, are smoking or have recently stopped smoking, and are taking any medications or supplements (eg, herbs, vitamins).
Exubera will be 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.
Accor?ding to the manufacturer, Exubera will be available for prescription by mid-year.
"I think there's a broad range of people who may benefit from Exubera," Dr Blonde says, noting that many patients with type 1 disease may prefer to take insulin in a noninjectable form.
"We do know that many people with type 2 diabetes who are advised to start insulin refuse it initially, so there can be a significant delay before they get optimal treatment," Dr Blonde adds. "Exubera represents a new option that may in?crease the acceptance of insulin. And increasing the number of people with type 2 diabetes who accept insulin may lead to improved blood glucose control and better outcomes with fewer complications," he concludes.