University of Vermont College of Medicine, Burlington, Vermont, USA. cefalu@pbrc.edu
OBJECTIVE: To comprehensively review the progress to date on the development of alternative routes for insulin delivery. RESEARCH DESIGN AND METHODS: Study data were collected through a Medline review. RESULTS: Proof of principle has been established for many routes of administration including dermal, nasal, oral, buccal, and pulmonary insulin delivery. CONCLUSIONS: Of all the approaches to date, pulmonary delivery appears to be most feasible. Ongoing phase III studies will ultimately determine safety, tolerability, and efficacy before approval for clinical use.