Darrell Hulisz, RPh, PhamD
Associate Professor, CWRU, School of Medicine
and David Peters
Doctor of Pharmacy Candidate, ONU College of Pharmacy
Inhaled insulin first made an appearance on the US market in 2011. The design of the metered dose device was cumbersome and lacked portability, was withdrawn by the manufacturer, Pfizer, with about a year. Recently, Sanofi began marketing a new inhaled insulin known as Afrezza®. The product has received FDA approval in both type 1 and type 2 diabetes.
Afrezza® is a human insulin product that is rapidly absorbed upon inhalation. Patients place a pre-filled cartridge containing either 4, 8, or 12 units of insulin into an inhaler. Patients exhale fully, then inhale sharply and hold their breath for as long as comfortable to get the medication absorbed. This creates a rapid absorption and a decreased duration of insulin action that more closely resembles endogenous prandial insulin release. The pharmacokinetic profile more closely resembles ultra-short acting insulin, such as insulin lispro or aspart.
In clinical trials for Type 1 diabetes, Afrezza® was found to be non-inferior to insulin when comparing patients' mean drop in HgbA1C. However, one trial found that patients taking injectable insulin were more likely to achieve a HgbA1C below 7% at the end of the 24 week trial period. In Type 2 diabetes, Afrezza® was studied to determine its viability as an add-on therapy in addition to oral diabetes medications. The clinical trial examined Afrezza® in combination with oral medication compared to oral medication alone. The group taking Afrezza® had greater diabetes control at the end of the trial period. While this is not a surprising finding, it does confirm its potential use as an add-on therapy for uncontrolled Type 2 diabetics.
The side effects associated with Afrezza® are similar to other insulin products. However, Afrezza® may cause acute bronchospasms or cough. This leads to several contraindications including patients who have asthma or COPD. Afrezza® was approved with a REMS program for prescribing that does require patients to have a thorough physical and a pulmonary function test on record before receiving it. While this will help protect those most at risk for bronchospasm with Afrezza®, post-marketing analysis will more clearly define the product's safety profile.
It's important to note that Afrezza® must be given at the beginning of a meal and, in patients with type 1 diabetes, must be used in combination with long-acting insulin. It may be considered an alternative to ultra-short acting insulin for patients with post-prandial hyperglycemia. However, the recommendation to rule out lung disease in every patient prior to use, as well as its potential high cost will likely limit the product's utility.
- AFREZZA® (insulin human [rDNA origin]) Inhalation Powder. http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm390865.pdf
- Afrezza® (insulin human) Inhalation Powder [package insert]. Bridgewater (NJ): Sanofi Aventis, October 2014.