Concept, Strategies, and Feasibility of Noninvasive Insulin Delivery

Abstract

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. Diabetes Care 27:239 -246, 2004T he therapeutic insulin era began on 11 January 1922 with the first clinical use of insulin by Banting and Best. In Ͻ2 years, insulin moved "from the realm of hypothesis to the reality of treatment" (1). In the ensuing 80 years, scientists uncovered the basic pathophysiology of diabetes, gradually elucidated insulin's structure, and focused their attention on developing better insulin formulations (e.g., NPH, lente). In this regard, the development and availability of rapid-acting (e.g., lispro, aspart) and basal insulins (e.g., glargine) have allowed for the routine use of very physiological insulin regimens.However, despite significant research, the first effective noninvasive delivery systems for insulin are only now in development, marking a new milestone in effective management of diabetes. There is a clinical need for such because insulin therapy is central to the treatment of people with type 1 diabetes. Intensive insulin therapy, in particular, is associated with better long-term clinical outcomes. The progressive decrease in ␤-cell function evident in the pathogenesis of type 2 diabetes means that the majority of patients will eventually fail on oral therapy and will require insulin therapy at some point. Furthermore, oral agent failure is just one of a number of situations where insulin therapy might be indicated in patients with type 2 diabetes (2).Despite the benefits of tight glycemic control, which ultimately can only be achieved with insulin in type 2 diabetic patients, there is reluctance on the part of physicians and patients to initiate insulin therapy (2). Factors such as weight gain, social stigma, lifestyle restriction, injection anxiety, sense of guilt or failure, and perception of worsening disease may affect patients' attitudes. Although hypoglycemia and weight gain are also perceived as barriers, these factors should not discourage the start of insulin. This reluctance contributes to poor glycemic control, and any advances that can help to minimize such concerns clearly have a place in diabetes management.NONINVASIVE INSULIN DELIVERY -Originally, insulin was administered intramuscularly. It soon became clear that subcutaneous injections were just as effective but considerably less traumatic (3). Over the years, researchers have suggested transdermal, ocular, oral, buccal, nasal, rectal, vaginal, and uterine delivery systems (3,4). However, subcutaneous administration has remained the route of choice,...

The Diabetic Lung - A New Target Organ?

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Effect of camel milk on glycemic control and insulin requirement in patients with type 1 diabetes: 2-years randomized controlled trial

“…Although conventional injectable insulin therapy meets this goal, it is associated with several therapeutic disadvantages, such as hyperinsulinemia, pain and inconvenience. Many attempts have been made to find alternative methods of insulin delivery through non-invasive routes (Owens, 2002;Gordberg and Gomez-Orellana, 2003;Cefalu, 2004). Among the alternative routes available for insulin delivery, oral administration is the most preferable, as it offers significant advantages in terms of therapeutic efficacy and patient acceptability.…”

Novel Concept in Pulmonary Delivery

“…Inhalation can represent the most favourable non-invasive route of administration for insulin (5.8 kDa) because insulin bioavailability can reach 37% following inhalation while it reaches at most 1% following oral, sublingual, nasal or transdermal administration without chemical enhancers (Cefalu, 2004;Illum, 2002). The first inhaled insulin product, Exubera®, was approved in January 2006 but withdrawn from the market already in October 2007 due to disappointing sales.…”