title: Inhaled insulin: a breath of fresh air? A review of inhaled insulin.
abstract: OBJECTIVE
  Despite many advances in diabetes care over the last century, some elements of insulin therapy remain inadequate for optimal care of the patient with diabetes. There is a need for improved pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues to mimic physiologic insulin secretion. In addition, a major barrier to successful insulin therapy has been patient resistance. Alternative routes of insulin administration, including inhaled insulin, have been under investigation for several years. This review discusses the rationale for pulmonary delivery of insulin, compares previous inhaled insulin products, reviews the literature on the safety and efficacy of a current inhaled insulin formulation under investigation, and compares this product with other prandial insulin products.
  
  
  METHODS
  English-language studies and reviews of inhaled insulin were searched in MEDLINE, the ClinicalTrials.gov registry (through May 2014), and the US Food and Drug Administration Website.
  
  
  RESULTS
  Inhaled insulin has several favorable characteristics due to pulmonary anatomy/physiology and the lack of injections. Pharmacokinetic and pharmacodynamic studies have shown a time-action profile suitable for prandial insulin use. Inhaled insulin seems to be safe and effective compared with other prandial insulin products and may be preferable to subcutaneous rapid-acting insulin analogues in terms of time-action profiles and rates of hypoglycemia. Small decreases in forced expiratory volume in 1 second (FEV1) have been shown with inhaled insulin, although this finding is not progressive over time and reverses with cessation of the medication.
  
  
  CONCLUSIONS
  Although several inhaled insulin products have been under investigation, only one (Exubera(®) [Nektar Therapeutics, San Carlos, California/Pfizer Inc, New York, New York]) was approved by the US Food and Drug Administration, and it was pulled from the market after only a short period of time. Technosphere(®) insulin (MannKind Corporation, Valencia, California) is currently the only inhaled insulin that remains under investigation. A review of the past and present literature on inhaled insulin is pertinent in understanding the current status of inhaled insulin and its risks and benefits. The current literature suggests that inhaled insulin could be a valuable option for prandial insulin administration, with a favorable risk to benefit ratio in some patients.
authors.affiliation: University of California, San Diego, San Diego, California. Electronic address: tksantos@ucsd.edu.
authors.forename: Tricia
authors.initials: T
authors.lastname: Santos Cavaiola
authors.affiliation: University of California, San Diego, San Diego, California.
authors.forename: Steven
authors.initials: S
authors.lastname: Edelman
mesh_terms: D000280:Administration, Inhalation; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: diabetes; glycemic control; inhalation; inhaled; insulin; pulmonary