Inhaled insulin therapy

The standard mode of insulin therapy has traditionally been by subcutaneous injection using disposable needles/syringes. However, other routes of administration, including continuous subcutaneous insulin infusion pumps and inhalation of finely powdered aerosolized insulin, are currently being explored. 

Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 1 diabetes. Diabetes Care 2004 27 2622-7. 

A.E. Mehta, J.L. Milburn, K.S. Hershon, J.L. Chiasson, and S.R. Levin. 2004. Efficacy and safety of inhaled insulin (exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes results of a 6-month, randomized, comparative trial. Diabetes Care 27 2356-2362. 

Since the first introduction of insulin to treat diabetic patients in 1923, much effort has been made to seek alternative convenient and painless routes for insulin administration instead of daily injections. In this respect the pulmonary route has received the most attention, and substantial evidence has shown inhaled insulin to be an effective, well-tolerated, noninvasive alternative route [53-56]. Insulin therapy is required for patients with type 1 diabetes. Although some patients with type 2 diabetes can control their disease with oral antidiabetics, many will eventually also require insulin. Thus, inhaled insulin shows promise for type 2 diabetic patients [54, 56]. There are two principal inhalation systems for insulin, namely aqueous solution and dry powder. The dry powder form (Exubera ) has been approved by FDA and the European Medicines Agency (EMEA) in January 2006. 

This chapter deals first with the therapeutic use of insulin and its analogues in TIDM as well as different ways of insulin administration, that is, by conventional intensified insulin therapy with multiple injections (MDl), pump treatment (CSII) and inhalation (INHI). 

Ceglia L, Lau J, Pittas AG. Meta-analysis efficacy and safety of inhaled insulin therapy in adults with diabetes mellitus. Ann Int Med 2006 145 665-675. 

The development of inhaled insulin must be seen in the light of a substantial resistance to insulin therapy in patients with type 2 diabetes and physicians who care for the patients. The reasons for this resistance include anticipated pain, inconvenience, fear of hypoglycaemia and weight gain [55,56]. 

Ereemantle N, Blonde L, Duhot D, Hompesch M, Eggertsen R, Hobbs FD et al. Availabihty of inhaled insulin promotes greater perceived acceptance of insulin therapy in patients with type 2 diabetes. Diabetes Care 2005 28(2) 427 28. 

Gross JL, Nakano M, Colon-Vega G, Ortiz-Carasquillo R, Ferguson JA, Althouse S, Tobian JA, Berclaz P-Y, Millicevic Z. Initiation of prandial insulin therapy with AIR inhaled insulin or insulin lispro in patients with type 2 diabetes a randomized noninferiority trial. Diabetes Technol Ther 2009 11 S27-34. 

Assess adherence to the prescribed regimen, including timing of inhaled medications with respect to airway clearance therapies and timing of enzymes and insulin with regard to meals. Is the patient taking any medications not prescribed by the CF center team ... 

Quattrin, T. 2004. Inhaled insulin recent advances in the therapy of type 1 and 2 diabetes. Expert Opinion on Pharmacotherapy. 5(12), 2597-2604. 

Hermansen K, Ronnemaa T, Petersen AH, Bellaire S, Adamson U. Intensive therapy with inhaled insulin via the AERx insulin diabetes management system. Diabetes Care 2004 27 162-7. 

In conclusion, the pulmonary delivery of insuhn offers an efficient and convenient therapy for diabetic patients. The feasibility of inhaled insuhn is based mainly on the lungs large absorption area of alveoli and their extremely thin walls full of intercellular spaces that make them more permeable than other mucosal sites to large proteins. Generally, inhaled insuhn showed a more rapid absorption than insulin administered by SC injection [59]. One major concern for pulmonary insuhn delivery is the unknown long-term effects of inhaled insuhn within the respiratory tract. Thus, possible long-term problems should be considered when insuhn is administered in this manner [66]. 

Barnett,A.H.,Dreyer,M.,Lange,P., and Serdarevic-Pehar, M. (2006), An open,randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (exubera) with glibenclamide as adjunctive therapy in patients with type 2 diabetes poorly controlled on metformin, Diabetes Care, 29,1818-1825. 

Rosenstock, J., Zinman, B., Murphy, L. J., et al. (2005), Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in type 2 diabetes A randomized, controlled trial, Ann. Intern. Med., 143, 549-558. 

The first half of the 20th century brought further attempts to use drugs and other therapies to treat mental illness. For example, tests were conducted on the effectiveness of giving amphetamines to depressed and narcoleptic patients, and carbon dioxide inhalation procedures were used in the treatment of illnesses referred to as psychoses and neuroses. Also used in the treatment of psychoses were antihistamines, insulin shock, and psychosurgery. Electroshock therapy was used to treat severe depression (a procedure still used today). Finally, in 1949 an Australian physician named John Cade discovered that the alkali metal lithuim successfully moderated manic conditions, although concerns about toxic reactions to it prevented its approval for use in the United States until 1970. Lithium remains a mainstay in the treatment of bipolar illnesses today. 

Insulin by Aerosol. Early studies showed that aerosolized insulin had a bioavailability of 57% after delivery via endotracheal tube into animals, about 10-fold higher than after instillation [125]. Human studies documented average time to peak insulin level at 40 min after aerosol inhalation by human diabetics and normalization of blood glucose [126]. Continuing research focuses on delivery systems [127-129] and particle modification [130,131] to enhance efficacy. Success of these new approaches will depend heavily upon their cost and convenience for patients. At this point, systems seem to depend upon nebulization, a distinct disadvantage for active people. Unless patients quickly recognize aerosolized insulin as distinctly superior to current therapy, e.g., subcutaneous insulin, the method will not gain acceptance. 

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