Key Words: Insulin,
Inhaled
Insulin is the most potent hypoglycemic agent available to the
date. Also it is the final resort to all type 2 Diabetes
mellitus (DM) patients and the only one for type1 DM patients.
Major drawback of insulin in long term treatment is the mode
of delivery, ie subcutaneous injections. Lot of research
and thoughts were there for development for alternate mode of
delivery of insulin.
The concept of inhaling insulin has been around for decades.
However, only in the late 1990 s could researchers make it
into a powder which can be inhaled through a device. The FDA
approved the first inhaled insulin, called Exubera, in
September 2006. Exubera was approved for both type 1 or
type 2 DM. Pfizer, the drug manufacturer took Exubera off the
market in October 2007 for financial reasons. The drug was
expensive and did not become popular with patients.
Quest for inhaled insulin continued, MannKind Corporation,
came out with Afrezza and FDA approved Afrezza in April 2014.
AFREZZA is rapid acting inhaled insulin indicated to improve
glycemic control in adult patients with diabetes mellitus.
Administration is using a single inhalation per cartridge. It
should be given at the beginning of a meal. AFREZZA is
available as single-use cartridges of 4 units and 8 units.
Dosing must be individualized. As this is prandial insulin,
basal insulin need to be continued.
The clinical data of Afrezza is from exposure of 3017 patients
which include 1026 patients with type 1 diabetes and 1991
patients with type 2 diabetes. The mean exposure duration was
8.17 months for the overall population
Afrezza has a Boxed Warning advising that acute bronchospasm
has been observed in patients with asthma and chronic
obstructive pulmonary disease (COPD). Afrezza should not be
used in patients with chronic lung disease, such as asthma or
COPD because of this risk. It is contraindicated in active
lung cancers. The most common adverse reactions associated
with Afrezza in clinical trials were hypoglycemia, cough, and
throat pain or irritation.
Assessment of pulmonary function (e.g., spirometry) before
initiating, after 6 months of therapy, and annually, even in
the absence of pulmonary symptoms is recommended. Great
caution should be exercised in patients with a history of lung
cancer or at risk for lung cancer. Preferably avoid the use in
diabetic ketoacidosis. Careful monitoring for other adverse
reactions common for any insulin like hypoglycemia,
hypokalemia, and fluid retention is required.
The FDA has asked for following post-marketing studies for
Afrezza to evaluate pharmacokinetics, safety and
efficacy in pediatric patients, a clinical trial to evaluate
the potential risk of pulmonary malignancy with Afrezza (also
assess cardiovascular risk and the long-term effect of Afrezza
on pulmonary function) and euglycemic glucose-clamp clinical
trials.
Prospects of inhaled insulin as an alternate route of drug
delivery are exciting; however real test of this molecule
would be the acceptance by patients and cost effectiveness.