INTRODUCTION: Delivery of therapeutic insulin via the pulmonary route has been 
the most investigated non-invasive alternative to the commonly used subcutaneous 
(SC) route for diabetes management. Despite discontinuation of the first 
inhalable insulin, Exubera®, due to suboptimal market acceptance, development of 
orally inhaled insulin delivery systems has been galvanized by the recent 
approval of Afrezza® and several others awaiting approval.
AREAS COVERED: The scope of this review article includes the prospects for and 
the challenges faced in developing inhaled insulin delivery systems; discussion 
of orally inhaled therapeutic insulin delivery systems that were discontinued, 
recently approved or are currently under active investigation; and formulation 
approaches that have the potential to deliver insulin via the pulmonary route.
EXPERT OPINION: The pulmonary route is the most advantageous route for 
non-invasive insulin delivery. Inhalable insulin therapeutics have the potential 
to be successful, provided that the formulations can be made with modified 
release patterns to substitute for both prandial and basal insulin injections, 
the delivery devices are convenient and easy to use, and the long-term safety of 
inhaled insulin is documented through extensive studies.