STEPS

New Drug Reviews

Insulin Inhalation Powder (Exubera) for Diabetes Mellitus

Am Fam Physician. 2007 May 15;75(10):1546-1547.

Insulin inhalation powder (Exubera), also called inhaled insulin, is a dry powder form of rapid-acting insulin delivered by oral inhalation. It is labeled for use in controlling hyperglycemia in adults with type 1 or type 2 diabetes mellitus.1 In patients with type 1 diabetes, inhaled insulin should be used in combination with a longer-acting insulin. In patients with type 2 diabetes, it can be used as monotherapy or in conjunction with oral agents or longer-acting insulin.

Name Starting dosage Dose form Approximate cost*

Insulin inhalation powder (Exubera)

Recommended dosing is based on the patient's body weight

Starter kit includes an inhaler, 180 1-mg blister packets, 90 3-mg blister packets, one replacement chamber, and two replacement release units

$188


*—Average wholesale cost, based on current Red Book, Montvale, N.J.: Medical Economics Data.

Name Starting dosage Dose form Approximate cost*

Insulin inhalation powder (Exubera)

Recommended dosing is based on the patient's body weight

Starter kit includes an inhaler, 180 1-mg blister packets, 90 3-mg blister packets, one replacement chamber, and two replacement release units

$188


*—Average wholesale cost, based on current Red Book, Montvale, N.J.: Medical Economics Data.

SAFETY

As with the use of other insulins, hypoglycemia is the primary safety concern with inhaled insulin. When used in combination with ultralente insulin, there was no clinically important difference in total or severe episodes of hypoglycemia per month compared with a combination of injected neutral protamine Hagedorn (NPH) insulin and regular insulin.24 However, as with injected insulin, hypoglycemia is much more likely to occur in patients using inhaled insulin plus oral agents compared with patients using oral agents alone (4.6 versus 0.1 episodes over three months).5

In rare instances, inhaled insulin can cause decreases in pulmonary function, which may be reversible upon discontinuation.1 Because absorption is variable, it should not be used in patients who smoke or those with lung disease (e.g., asthma, chronic obstructive pulmonary disease).1 Inhaled insulin is U.S. Food and Drug Administration pregnancy category C.1

TOLERABILITY

Cough, nonspecific chest pain, dyspnea, and dry mouth occur in less than 5 percent of patients started on inhaled insulin; however, few persons will discontinue treatment as a result.1 Patients receiving inhaled insulin generally prefer this route of administration compared with subcutaneous administration.6 In clinical trials, weight gain in patients using inhaled insulin was similar to weight gain in patients using subcutaneous insulin.1,2,4

EFFECTIVENESS

The onset of action is similar to that of rapid-acting subcutaneous insulin analogues, but the duration of action, which is similar to that of regular insulin, is longer.1 Inhaled insulin has been compared with subcutaneous regular insulin in combination with a long-acting or intermediate-acting insulin in patients with type 1 or type 2 diabetes. These effectiveness studies ranged from three to six months in duration.24

Patients will experience similar decreases in A1C levels compared with those treated with subcutaneous regular insulin.24 In patients with type 2 diabetes, inhaled insulin will decrease A1C levels by 1.4 to 1.9 percent when added to or substituted for existing oral agent therapy.5 It will decrease postprandial blood glucose by 21 to 30 mg per dL (1.2 to 1.7 mmol per L) and fasting blood glucose by 20 to 35 mg per dL (1.1 to 1.9 mmol per L).24

Inhaled insulin has not been compared with rapid-acting subcutaneous insulin analogues, but it has been compared with oral agents for diabetes mellitus, specifically sulfonylureas, thiazolinediones, and biguanides.57 Its effect on diabetes-related complications and mortality has not been evaluated.

PRICE

The inhaled insulin starter kit, which is intended to be a one-month supply, costs approximately $188. The refill combination pack 12 costs approximately $140 and includes 90 1-mg blisters and 90 3-mg blisters (equivalent to 990 units of rapid-acting insulin). The combination pack 15 costs approximately $175 and includes 180 1-mg blisters and 90 3-mg blisters (equivalent to 1,260 units of rapid-acting insulin). One 10-mL vial (1,000 units) of insulin lispro (Humalog) or insulin glulisine (Apidra) costs approximately $78, and one 10-mL vial of insulin aspart (Novolog) costs approximately $84.

SIMPLICITY

Inhaled insulin is dosed in milligrams. The initial premeal treatment dose is based on body weight (0.05 mg per kg), and the optimal administration time is no more than 10 minutes prior to meals.1 Subsequent dose adjustments, which are based on patient response, have to be made in increments of 1 and 3 mg (equivalent to 3 and 8 units of regular insulin), with each dose inhaled separately via the insulin inhaler. The inhaler is bulky and requires hand strength and dexterity for the user to release the dose. Additionally, the inhaler device must be replaced yearly, and the release unit within the device must be replaced bimonthly.

Pulmonary function should be monitored during treatment. The manufacturer suggests baseline spirometry followed by repeat testing at six months and one year, with yearly follow-up thereafter.1

Bottom Line

Inhaled insulin provides an alternative route of administration for rapid-acting insulin but offers no other benefit over available insulin therapy. It may reduce, but not eliminate, the need for self-injection in patients with type 1 diabetes. In patients with type 2 diabetes, the risk of hypoglycemia significantly increases when inhaled insulin is added to or substituted for oral agents. Inhaled insulin has the potential to cause pulmonary adverse effects and is more expensive than rapid-acting insulin analogues. For these reasons, inhaled insulin should be reserved for use as alternative therapy for those who fail or are intolerant to other treatments.

Address correspondence to Nancy Borja, PharmD, at nborja@nova.edu. Reprints are not available from the authors.

Author disclosure: Nothing to disclose.

REFERENCES

1. Exubera (insulin human [rDNA origin]) inhalation powder [Product information]. New York, N.Y.: Pfizer Labs, January 2007. Accessed February 23, 2007, at: http://www.pfizer.com/pfizer/download/uspi_exubera.pdf.

2. Skyler JS, Weinstock RS, Raskin P, Yale JF, Barrett E, Gerich JE, et al., for the Inhaled Insulin Phase III Type 1 Diabetes Study Group. Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects: a 6-month, randomized, comparative trial. Diabetes Care. 2005;28:1630–5.

3. Quattrin T, Belanger A, Bohannon NJ, Schwartz SL, for the Exubera Phase III Study Group. 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;27:2622–7.

4. Hollander PA, Blonde L, Rowe R, Mehta AE, Milburn JL, Hershon KS, 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;27:235662.

5. Rosenstock J, Zinman B, Murphy LJ, Clement SC, Moore P, Bowering CK, 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;143:54958.

6. Barnett AH, Dreyer M, Lange P, Serdarevic-Pehar M. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with metformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea. Diabetes Care. 2006;29:12827.

7. Barnett AH, Dreyer M, Lange P, Serdarevic-Pehar M. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with glibenclamide as adjunctive therapy in patients with type 2 diabetes poorly controlled on metformin. Diabetes Care. 2006;29:181825.

STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer.

The series coordinator for AFP is Allen F. Shaughnessy, PharmD, Tufts University Family Medicine Residency Program, Malden, Mass.


Copyright © 2007 by the American Academy of Family Physicians.
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