Afrezza (Insulin Human) Inhalation Powder: A New Inhaled Insulin for the Management Of Type-1 or Type-2 Diabetes Mellitus.

According to the National Diabetes Statistics Report, 29.1 million people have diabetes mellitus (DM) in the U.S., or approximately 9.3% of the population.1 DM imposes a financial burden on both patients and the health care economy, with direct and indirect costs totaling $245 billion in 2012.1 All patients with type-1 DM (T1DM) require insulin therapy. Patients with type-2 DM (T2DM) may also become dependent on exogenous insulin as their disease progresses.2 Approximately 6 million people in the U.S. require insulin therapy.1 Insulin therapy allows for better glycemic control, but patients are often hesitant to make the transition to insulin because of its adverse-event profile (e.g., hypoglycemia, weight gain) and because of fear of injections.3 Since injectable insulin was introduced into clinical practice in 1922, other routes of administration have been explored.4 Inhaled insulin, for example, offers the advantage of a larger area of absorption—approximately 70 to 140 square meters, or half of a tennis court.4 In 1924, the first study of inhaled insulin was conducted in human subjects at doses 30 times higher than that of the subcutaneous (SC) route of administration.4,5 In 2006, the Food and Drug Administration (FDA) approved the first inhaled insulin for patients with T1DM or T2DM. Exubera (Nektar Therapeutics/Pfizer) was derived from recombinant human insulin (rDNA origin), with a bioavailability of approximately 60%.4,6 It was available as a spray-dried insulin powder packaged in blisters containing 1 mg or 3 mg of insulin.6 Despite the promise of a new delivery system, Exubera did not find a profitable niche in the insulin market. Twenty-one months after its approval, the product was voluntarily withdrawn from the market because of low sales.7 The failure of Exubera may have resulted from several factors, including the high cost of the inhaler; dosing in milligrams, which may have confused patients who had been receiving conventional insulin therapy that was measured in units; the large size of the device; and an FDA warning regarding the potential for primary lung cancer.7,8 Novel strategies for the administration of inhaled insulin continued to be investigated, and in July 2014 the FDA approved Afrezza (insulin human) inhalation powder (MannKind Corp./Sanofi-Aventis US) for patients with T1DM and T2DM.9 Afrezza employs the new Gen2 inhaler (Figure 1), which is smaller and easier to use than the previously available Exubera device.10–12 Figure 1 Afrezza Insulin Inhaler12 This article reviews the pharmacology, pharmacokinetics, drug interactions, clinical efficacy, dosage and administration, safety profile, and place in therapy of Afrezza.