Intranasal insulin: PK profile designed specifically for prandial treatment of Type 2 Diabetes

Insulin is the most effective therapy for lowering glycosylated hemoglobin (A1c) levels in Type 2 diabetics, and yet it is typically the last therapeutic option employed. Currently, the vast majority of marketed prandial insulin products require frequent injections, which may be a barrier among patients and physicians to initiating this medically important therapy. Beyond the inconvenience, concerns about potential weight gain and hypoglycemia may also limit the early use of insulin therapy. None of the approved insulin formulations (including rapid‐acting products) provide a PK response fast enough to mimic the endogenous first‐phase insulin release that is seen following bolus intravenous glucose infusion and that is associated with downregulation of gluconeogenesis. Delayed absorption of insulin from subcutaneous injection results in a relatively broad plasma insulin peak and a prolonged duration of action, potentially increasing the risk of hypoglycemia. We are developing an intranasal insulin formulation that provides a well‐tolerated and efficient means of delivering prandial insulin more rapidly than fast‐acting injectable insulin. With its fast onset and short duration of action, Nastech's intranasal insulin exhibits pharmacokinetic and pharmacodynamic properties that take advantage of the known benefits of delivering a rapid and transient burst of insulin at mealtime. This review discusses the current development of intranasal formulations and compares the characteristics of intranasal insulin to other non‐invasive insulin delivery efforts, including pulmonary, oral, and transdermal formulations. Drug Dev Res 69:143–152, 2008. © 2008 Wiley‐Liss, Inc.