Pharmacology Update

Insulin Human Inhalation Powder (Exubera®)

By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.

The fda has approved the first non-injectable insulin for the treatment of type 1 and type 2 diabetes. Marketed under the trade name Exubera®, the new insulin product is a dry powder inhalation delivery system that uses the vascular system of the alveoli to deliver insulin into the blood stream. Exubera® is licensed from Nektar Therapeutics and will be marketed by Pfizer Labs.


Inhaled insulin powder is indicated for the treatment of adult patients with type 1 and type 2 diabetes mellitus. For type 1 patients inhaled insulin should be used with a longer-acting insulin.1


The administration timing of inhaled insulin (INH) is similar to injectable short-acting insulin (ie, immediately before meals and no more than 10 minutes prior). A 1 mg blister of inhaled insulin is approximately equivalent to 3 IU of injected regular human insulin. A 3 mg blister corresponds to 8 IU and 6 mg to 16 IU of regular insulin. Initial pre-meal dose may be calculated by multiplying the body weight in kg by 0.05. The product is rounded down to the nearest whole milligram number.1

INH is supplied as 1 mg and 3 mg blisters.

Potential Advantages

Inhaled insulin provides a non-invasive delivery of insulin. Compared to the injection, inhaled insulin had greater acceptance in terms of convenience and patient satisfaction.2,3 INH is rapidly absorbed and is independent of BMI.1

Potential Disadvantages

INH is contraindicated in patients who smoke or who have discontinued smoking < 6 months prior. Systemic exposure to insulin is significantly greater in smokers than non-smokers. Absorption is reduced by 20-30% in patients exposed to passive cigarette smoke. INH is not recommended in patients with underlying lung disease.1 Higher frequencies of cough and increase in insulin serum antibodies have been associated with INH.2-5 INH has been associated with a decline in pulmonary function specifically FEV1 and carbon monoxide diffusing capacity.1 A decline in FEV1 from baseline of 20% occurred in 1.5% of patients compared to 1.3% for the comparator group. A decline of 20% in DLCO occurred in 5.1% of the INH group compared to 3.6% for the comparator group. Pulmonary function should be performed before initiation of therapy, after 6 months, and annually thereafter.1

In patients who need basal insulin, INH does not eliminate this requirement. The long-term effect on insulin on lung structure and function is not known.


Inhaled insulin is delivered in small particles (1-5 m) and absorbed via the alveolar capillary bed by trancytosis. INH is absorbed at a more rapid rate than subcutaneous (SQ) insulin. Maximum serum concentration is 24 minutes for INH vs 106 minutes for SQ insulin.7 The efficacy of INH compared to SQ regular insulin was determined in 2 phase III studies in type 1 diabetics (n = 663) and 1 study in type 2 diabetics (n = 299). These noninferiority studies were powered to detect a treatment difference in HbA1c of 0.5%.6 No significant differences in change in HbA1c were observed between treatments. A greater decrease in fasting blood glucose was seen with INH.2,3,8 Type 2 patients on SQ insulin can be switched to INH while maintaining HbA1c levels.7 INH can be effectively added to, or substituted for, oral therapy or in patients inadequately controlled on diet or oral regimens.8,9 Overall risk of hypoglycemia was similar between groups although a higher rate of severe hypoglycemia was reported with INH in one study.4 Patient satisfaction and quality of life favored INH. The clinical relevance of insulin antibodies is not clear, as these do not appear to impair postprandial glucose tolerance, affect the pharmacodynamics of insulin, or affect tolerability.5 The cost of INH was not available at the time of this review.

Clinical Implications

INH provides a noninvasive delivery of insulin. Since the long-term effects of INH are not known, subcutaneous insulin remains the preferred route of administration.


1. Exubera Product Information. Pfizer Labs. January, 2006.

2. Quattrin T, et al. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 1 diabetes: results of a 6-month, randomized, comparative trial. Diabetes Care. 2004;27:2622-2627.

3. Hollander PA, et al. Efficacy and safety of inhaled insulin (exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes: results of a 6-month, randomized, comparative trial. Diabetes Care. 2004;27:2356-2362.

4. Skyler JS, et al. Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects: a 6-month, randomized, comparative trial. Diabetes Care. 2005;28:1630-1635.

5. Heise T, et al. The effect of insulin antibodies on the metabolic action of inhaled and subcutaneous insulin: a prospective randomized pharmacodynamic study. Diabetes Care. 2005;28:2161-2169.

6. Odegard PS, Capoccia KL. Inhaled insulin: Exubera. Ann Pharmacother. 2005;39:843-853.

7. FDA Statistical Review and Evaluation. December, 2004.

8. Rosenstock J, et al. Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2005;143:549-558.

9. DeFronzo RA, et al. Efficacy of inhaled insulin in patients with type 2 diabetes not controlled with diet and exercise: a 12-week, randomized, comparative trial. Diabetes Care. 2005;28:1922-1928.