The recent approval of human insulin inhalation powder (Exubera) by the FDA creates a new therapeutic option for people with type 1 and type 2 diabetes. The drug is the first inhaled, noninjectable insulin option available in the United States. The approval was based on studies of more than 2500 patients who were enrolled for 12 weeks to 6 months. The results of the studies showed that inhaled insulin was as effective as short-acting injectable insulin for achieving glycemic control in adults with type 1 and type 2 diabetes. Addition of inhaled insulin to oral medications in type 2 diabetes also resulted in better glucose control in patients who were poorly controlled on oral agents alone.^1-3

Inhaled insulin has a duration of activity that is similar to injectable regular insulin but has an onset of action that is similar to rapid-acting insulin analogs. Pharmacokinetic studies demonstrated peak insulin levels at an average of 49 minutes for inhaled insulin versus 105 minutes with regular insulin.^4,5 The drug is dosed at 0.05 mg/kg, rounded down to the nearest milligram. Patients should administer inhaled insulin 10 minutes prior to meals using the appropriate combination of 1-and 3-mg unit doses that equal their calculated dose. Inhaled insulin should be administered only with the inhaler that is provided with the product, and any other inhaled medications should be administered before the insulin. Three 1-mg doses cannot be substituted for the 3-mg capsule. Doing so results in an insulin exposure that is 30% to 40% higher than that of the 1-and 3- mg combination. Patients with type 1 diabetes should use inhaled insulin in combination with long-acting injectable insulin. Patients with type 2 diabetes may use the product as monotherapy or in combination with oral agents.

The potential for inhaled insulin to cause long-term respiratory problems is a concern that delayed approval of the product in the United States. The proposed mechanism of damage is longterm inhalation and deposition of protein on the lung surface. Recent short-term studies have not shown any clinically significant changes in lung function, however.^1-4 Use of the inhaled product is not recommended in patients who have chronic lung diseases (asthma, bronchitis, or emphysema). It is contraindicated in patients with poorly controlled or unstable lung disease, because variations in lung function can affect absorption and increase the risk for hypoglycemia or hyperglycemia. Blood glucose should be monitored closely during respiratory illnesses that occur while inhaled insulin is being used. The manufacturer recommends baseline lung function tests (LFTs) at the beginning of treatment. A small, clinically insignificant decrease in lung function may occur in the first few months of treatment, so LFTs should be repeated at 6 months of therapy. If test results are stable, LFTs may be repeated annually. Patients who have a decline of 20% or more from baseline forced expiratory volume in 1 second should discontinue treatment.⁵ Long-term postmarketing studies will be conducted to further investigate effects on lung function.

Other concerns exist with the use of inhaled insulin related to precision of dosing, when compared with injection and induction of antibodies to insulin when it comes in contact with the lung surface. Comorbidities, smoking status, and administration technique have the potential to greatly affect exposure to the drug and possibly the clinical results achieved with the new formulation. Injection of insulin minimizes variation seen in insulin levels, but many patients are afraid of injections and the possibility of hypoglycemia and will refuse to use injectable insulin. With respect to antibody development, studies demonstrated a 28-fold increase in antibodies during treatment, but this increase did not translate into changes in plasma glucose or duration of action of inhaled insulin when compared with the subcutaneous injection of insulin.⁶

Inhaled insulin is contraindicated for patients who smoke or who have quit smoking in the past 6 months. A study of pharmacokinetics in smokers concluded that the time to maximum concentration of insulin and the area under the curve (AUC) for smokers were higher, greatly increasing the risk of hypoglycemia.⁷ These 2 parameters were unaffected by smoking when subcutaneous insulin was used. After the cessation of smoking, the AUC of inhaled insulin decreased by 50% within 1 week. Resumption of smoking completely reversed the effects of smoking cessation. Treatment should be discontinued in patients who start or resume smoking because of this risk.

Adverse events associated with inhaled insulin are generally mild to moderate. Some patients may experience coughing after product inhalation, but these episodes tend to improve as treatment continues. Other than cough, hypoglycemia, dyspnea, sore throat, and dry mouth were the most commonly reported side effects.

Dr. Garrett is a clinical pharmacist practitioner at Cornerstone Health Care in High Point, NC.

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