Is Inhaled Insulin A Viable Alternative For Patients With Diabetes?

By Jennifer Pahira and John S. Steinberg, DPM

     According to the International Diabetes Federation (IDF), diabetes affects more than 230 million people worldwide and is expected to affect 350 million by 2025. Controlling blood glucose levels via subcutaneous injections of insulin has been a key clinical intervention for many people. While injected insulin has proven to be a reliable intervention, it is met with significant resistance by patients who want to avoid the stigma and pain associated with this therapy.      Over the years, extensive research has been conducted in an effort to develop a less invasive and more patient-satisfactory means of insulin delivery. The approval of inhaled insulin could prove to be the first of many milestones in an attempt to make treatment delivery more acceptable to the patient.      In January, the FDA approved Exubera (manufactured by Pfizer in collaboration with Nektar Therapeutics) for adults with type 1 or type 2 diabetes in both the United States and Europe. Exubera is short-acting inhaled insulin and can be absorbed faster than subcutaneous injection of insulin. The insulin comes in an inhaler weighing about 4 oz. It can be stored at room temperature and has a 24-month shelf life. The Exubera inhaler produces a cloud of insulin powder in a clear chamber visible to the patient. The insulin powder passes rapidly into the bloodstream to regulate the body’s blood sugar levels. Patients should take it before meals.1      Historic difficulties in the development of an oral or inhaled insulin have included getting the insulin past the acidity of the stomach and digestive enzymes in the intestines, and opening the intestine for insulin transportation. Inhaling the insulin through the nose was ruled out because too much insulin was needed to pass through the mucus membranes. (In order to deliver 10 units into the blood, the patient must inhale 100 units.) Another detriment was the fact that enhancing transportation of the insulin with chemicals resulted in irritation of the nasal passages. This research concluded that inhaling the insulin directly into the lungs through the mouth would have the most potential.      Inhale Therapeutic Systems has worked to create an insulin particle that would meet the needs of inhalation through the mouth. The particle developed is small enough to be inhaled and flow past the throat into the lungs but is large enough that the patient does not exhale the particles back into the air. One issue that is still under investigation is the precise control of how much insulin the patient is taking in. Precision is critical for all patients with diabetes. Therefore, long-acting insulin is still necessary for basal coverage of insulin requirements.

What The Research Reveals

     Although inhalation directly into the lungs seems to be a promising new clinical approach for insulin delivery, there are some concerns regarding the long-term effects of growth protein inhalation on the lungs.      However, in a 2004 study conducted by Pfizer Global Research and Development, investigators noticed similar improvements in hemoglobin A1c levels and average changes in pulmonary function in separate patient groups taking inhaled or injected insulin. Overall, patients reported increased comfort and ease of use with inhaled insulin as compared to injection.      Another study reported in the Archives of Internal Medicine confirmed similar results in people with type 2 diabetes who took either a combination of short-acting inhaled insulin and long-acting injected insulin, or took injected insulin alone. Researchers concluded that the addition of one to two pre-meal inhalation doses improved glycemic control without the need for additional subcutaneous injections.2      As reported by the American Diabetes Association, events of mild hyperglycemia are lowered slightly among people who inhale insulin. A six-month trial done by Hollander, et. al., studied a group of men and women between the ages of 35 and 80 with type 2 diabetes who had a history of taking at least two insulin shots daily.3 One treatment group took inhaled insulin pre-meal along with one dose of long-acting injected insulin at bedtime and the other took two daily shots of injected insulin alone.      Confirming previous studies, investigators found lowered hemoglobin A1c levels in both patient groups. Additionally, hyperglycemia was slightly lower among inhaled insulin patients (1.4 events per patient per month) with no differences in severe episodes.3

Some Caveats You Should Keep In Mind

     The FDA has not approved Exubera for children or teens. Additionally, smokers are discouraged from using Exubera because more of the insulin is able to enter the body through the lungs and could cause an overdose. Interestingly, researchers found that smokers who utilized inhaled insulin had a higher systemic absorption while non-smokers who were exposed to secondhand smoke had a lower systemic absorption. Inhaled insulin may perform differently in other patients with pulmonary diseases such as asthma, bronchitis or chronic obstructive pulmonary disease. The known side effects at this time are coughing, shortness of breath, sore throat and dry mouth.      Exubera was expected to be widely available on the shelves of pharmacies in late summer of 2006. Early cost comparisons put the price of inhaled insulin at approximately three times that of traditional injected forms. Although pricing may be modified by Pfizer along the way, there is concern that this high cost could create some challenging coverage and formulary battles with health insurance plans, etc.

In Conclusion

     Many people need short acting insulin before meals in order to cope with the spike in blood sugars caused by eating. As a possible alternative to avoiding injections before every meal, the short-acting inhaled insulin delivery method maintains glycemic levels while keeping the person comfortable. By providing a less invasive option, one would hope to achieve better patient compliance to dosing regimens. Although long-acting insulin injections are still required, Exubera and future inhaled insulin may provide patients with a painless solution to multiple pre-meal injections. Pahira is a second-year undergraduate student at the University of Pennsylvania. Dr. Steinberg (pictured) is an Assistant Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C. He is a Fellow of the American College of Foot and Ankle Surgeons. Editor’s note: For related articles, see “Can An Exercise Pill Enhance Blood Glucose Control?” in the January 2004 issue, “Proactive Measures To Prevent Diabetic Complications” in the October 2005 issue or visit the archives at



1. Nektar Therapeutics.
2. Weiss SR, et. al. Inhaled Insulin Provides Improved Glycemic Control in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Agents. Archives of Internal Medicine 163(19). 2003.
3. Hollander PA, et. al. Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 2 Diabetes. Diabetes Care. 27:2356-2362, 2004.
Additional References
4. Skyler JS, et. al. American Diabetes Association. Diabetes Care 28:1630–1635, 2005.
5. DeNoon D. WebMD Medical News.
6. International Diabetes Federation.
7. Walsh J. Will It Really Take Your Breath Away? 2006.
8. Medical News Today. Inhaled insulin controls diabetes over long term. MediLexicon International Ltd. 2004.
9. D’Arrigo T. Inhaled Insulin is on The Way. Diabetes Watch, 2006.


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