Inhaled Insulin—It Is Coming!January 11, 2017 /
Afrezza® is the new inhaled insulin product recently approved for use in the United States under the risk evaluation and mitigation strategy. Launch is planned for the beginning of 2015. An agreement was signed between MannKind (the manufacturer) and Sanofi (a multinational pharmaceutical company).
Afrezza is a rapid-acting human insulin powder that is inhaled for the treatment of either type 1 or type 2 diabetes. It is administered at the start of a meal or within 20 minutes of starting a meal, with peak insulin levels achieved within 12 to 15 minutes of administration and decline to baseline by approximately 180 minutes after inhalation. Afrezza is active for a shorter amount of time than rapid-acting insulin, so it is likely to more closely replicate what the pancreas is supposed to do.
Individuals with type 1 diabetes cannot use Afrezza by itself—it requires use in combination with a long-acting insulin. It seems that Afrezza is less likely to cause weight gain or severe hypoglycemia, compared to standard insulin or sulfonylureas. In a study comparing Afrezza with NovaLog®, patients receiving Afrezza had almost one-half the number of severe hypoglycemia episodes, and they actually lost weight compared with the NovaLog recipients who gained weight.
Afrezza will have a boxed warning advising that acute bronchospasm was observed in patients with asthma and chronic obstructive pulmonary disease. Afrezza is not recommended for the treatment of diabetic ketoacidosis or for patients who smoke.
The US Food and Drug Administration (FDA) requires four postmarketing studies as a condition of approval:
- Evaluation of the pharmokinetics, safety, and efficacy of Afrezza in pediatric patients
- Assessment of the potential risk for pulmonary malignancy or cardiovascular risk with Afrezza and long-term effect on pulmonary function
- A pharmokinetic euglycemic glucose clamp clinical trial characterizing dose response
- A pharmokinetic euglycemic glucose clamp clinical trial within subject variability
Efficacy and safety data for Afrezza came from studies involving a total of 3017 patients (1026 with type 1 diabetes and 1991 with type 2 diabetes). After 24 weeks of use, Afrezza reduced A1c levels by 0.4% in both groups. However, A1c reduction was not as good as that from insulin aspart among the type 1 patients. However, it was significantly superior to placebo among type 2 patients who also were taking oral diabetes medications.
The most common adverse reactions associated with Afrezza were:
- Throat pain/irritation
Another inhaled insulin, Exubera®, was approved in 2006 and pulled from the market in 2007 because of low uptake. However, the inhaler for Afrezza is much smaller than the one used with Exubera. Because inhaled insulin comes in a powder, the FDA requires dosing by weight, not by unit. This was incredibly confusing, because other forms of insulin are dosed in units. However, Afrezza is said to have much simpler dosing than Exubera did. Exubera was available in 1-milligram (mg) and 3-mg cartridges, yet the contents of three of the 1-mg cartridges did not exactly equal the contents of the 3-mg cartridge. With Afrezza, the dosing is in units, with a 4-unit cartridge and an 8-unit cartridge.
References and recommended readings
Doheny K. Inhaled insulin: what to tell patients. Medscape website. http://www.medscape.com/viewarticle/827637?src=wnl_edit_specol&uac=214376ET. Published July 1, 2014. Accessed February 25, 2015.
Mintz M. Is inhaled insulin a ‘game changer’? Medscape website. http://www.medscape.com/viewarticle/828463?src=wnl_edit_specol&uac=214376ET. Published July 23, 2014. Accessed February 25, 2015.
Nainggolan L. Deal with Sanofi means inhaled insulin on US market in 2015. Medscape website. http://www.medscape.com/viewarticle/829687?src=wnl_edit_specol. Published August 11, 2014. Accessed February 25, 2015.
Tucker M. FDA approves inhaled insulin Afrezza for diabetes. Medscape website. http://www.medscape.com/viewarticle/827539?src=wnl_edit_specol&uac=214376ET. Published June 27, 2014. Accessed February 25, 2015.