Intranasal insulin therapy: the clinical realities

Hilsted, J.; Madsbad, Sten; Hvidberg, A.; Rasmussen, Michael Højby; Krarup, Thure; Ipsen, Hans-Henrik; Hansen, Birthe; Pedersen, Maria; Djurup, R.; Oxenbøll, B

doi:10.1007/bf00401839

Cited by 74 publications

(25 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a previous study, we showed that inhalation of an insulin powder aerosol containing solid insulin particles (99 U) led to a relative bioavailability of 7.8 ± 3.5% and a relative bioefficacy of 7.6 ± 2.9% (2). This bioefficacy was comparable with that achieved with nasal insulin administration using absorption enhancers but implies that a large amount of insulin has to be used with either administration form to achieve a sufficient metabolic effect (3)(4)(5)(6)(7). Nevertheless, the time-action profile seen with inhalation of insulin showed promising properties (i.e., a rapid onset of action and a relatively long duration of action).…”

mentioning

confidence: 79%

Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer.

et al. 2000

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 79%

Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer.

et al. 2000

View full text Add to dashboard Cite

show abstract

“…However, a study involving 31 subjects with type 1 diabetes found that the intranasal insulin dose needed to reach given markers of glycemic control was some 20 times higher than that of subcutaneous administration. Moreover, serum insulin concentrations increased more rapidly and declined more quickly during nasal administration than during subcutaneous administration (16). The authors concluded that intranasal insulin treatment was not a realistic alternative to subcutaneous insulin because of the low bioavailability and high rate of treatment failure.…”

Section: Intranasalmentioning

confidence: 99%

Concept, Strategies, and Feasibility of Noninvasive Insulin Delivery

Cefalu

2004

Diabetes Care

149

View full text Add to dashboard Cite

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,...

show abstract

“…NovoNordisk made the first major attempt to bring a non-injectable insulin to market with nasal insulin. Experience soon showed that this was not a realistic alternative, for despite the advantage of rapid absorption, bioavailability was low (the nasal dose needed to be 20-fold greater than the injected dose) and the rate of treatment failure unacceptably high [7]. The success of insulin pens may also help to explain why the project was quietly dropped.…”

Section: Dangerous Safetymentioning

confidence: 99%