Inhaled Rapid Acting Insulin- Redux

Dr. Fran Cogen Health Pro
  • AFREZZA® has been approved by the FDA (Food and Drug Administration) for use in adults. What is AFREZZA?


    AFREZZA is an “ultra rapid- acting mealtime insulin” that has been developed for adults with type 1 and 2 diabetes to improve glycemic control. The system includes an inhaler device that consists of AFREZZA inhalation powder “single-use dose cartridges.” The inhaled powder is administered at the start of a meal and according to the MannKind Corporation, “it dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak levels of insulin are achieved within 12-15 minutes after administration.” (http://www.mannkindcorp.com/product-pipeline-diabetes-afrezza.htm).

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    According to Mannkind, clinical trials involving more than 6,500 adults demonstrated the following:

    • Proven reduction in Hhb A1c

    • Reduced risk of hypoglycemia versuss. rapid-acting analogs

    • Less weight gain versuss. rapid -acting analogs

    • Injection- free insulin delivery.

    The FDA provided the following information for the completed follow-up study for AFREZZA. The FDA evaluated the safety and effectiveness of the inhaled insulin in 3,017 adult subjects (1,026 with type 1 diabetes and 1,991 with type 2 diabetes). The studies compared the efficacy of AFREZZA administered at meals in adults with type 1 diabetes to aspart--both in combination of basal insulin over a 24-week study.

     

    At week 24, patients receiving basal insulin and AFREZZA at meals provided an average reduction of Hb A1c of 0.4 percent. However, AFREZZAprovided less Hb A1c reduction than the rapid-acting insulin aspart (Novolog®), and the difference was statistically significant.

     

    In type 2 patients using oral medications, the efficacy of AFREZZA at mealtime was compared to a placebo inhalation over 24 weeks. At week 24, treatment with AFREZZA in addition to the oral medications demonstrated a statistically significant decrease in Hb A1c as compared to the Hb A1c in the placebo group.

     

    It is important to note that AFREZZA cannot be used in place of basal or long-acting insulin and must be used in as the rapid-acting component in basal/bolus regimens in type 1 diabetes. The FDA also admonishes that AFREZZA should not be used in the treatment of diabetic ketoacidosis or in patients who smoke.

     

    Major limitations of AFREZZA include a warning that acute bronchospasm (wheezing) has been observed in patients with asthma and Chronic Obstructive Pulmonary Disease (COPD). As such, AFREZZA is contraindicated in patients with chronic lung disease. Common side effects in the studies include hypoglycemia, cough, and throat pain.

     

    The FDA is still requiring further post-marketing studies for evaluation of AFREZZA. These include:

    • Aa clinical trial to evaluate pharmacokinetics, safety, and efficacy in pediatric patients.” (So, NOT approved for kids yet).

    • A clinical trial to evaluate potential risk of pulmonary malignancy with AFREZZAAfrezza.”

    • Ttwo pharmacokinetic-pharmacodynamic euglycemic glucose-clamp clinical trials to characterize dose-response and one to characterize within -subject variability.” (These trials are routinely performed on all drug studies).

    This inhaled insulin is the newest “inhaled” product on the block. Previously, Exubera® was the inhaled insulin of choice and subsequently was discontinued and removed from the market due to lack of general adoption and structural pulmonary problems related to long-term use. Also, restriction of the AFREZZA product for people with pulmonary issues such as asthma and COPD is significant as these are very common chronic illnesses both in children and adults. We should also consider how AFREZZA would work in the presence of upper respiratory infections, bronchitis, or pneumonia. I imagine it will be quite difficult to tritrate dosing due to inflammation, wheezing, and pulmonary infiltrates.

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    Clearly, though very intriguing, the verdict as to long-term application of the short-acting inhaled insulin, AFREZZA, is yet to be determined.

Published On: July 08, 2014