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Submitted on November 15, 2004
Accepted on February 22, 2005
Indiana University School of Medicine, Indianapolis, IN, USA; Pfizer Global Research and Development, Groton, CT, USA
* To whom correspondence should be addressed. E-mail: efineber{at}iupui.edu.
Objective
To compare antibody responses to inhaled human insulin vs. sc human insulin and to determine if insulin antibody binding is associated with adverse clinical consequences.
Research Design andMethods
Insulin antibody data from initial phase II/III trials were analyzed comparing the efficacy and safety of inhaled insulin with various agents, including sc insulin. Additionally, data from a 24-month extension of the phase III studies were examined. Data were pooled into the following three groups based on insulin treatment status at baseline: patients with type 1 diabetes, patients with type 2 diabetes insulin-using and non-insulin-using at baseline. Immunoglobulin class analysis was also performed on randomly selected sera from type 1 patients at the end of the initial trials.
Results
In the initial trials, greater insulin antibody binding was observed in patients receiving inhaled insulin vs. sc insulin. The greatest antibody responses to inhaled insulin were observed in patients with type 1 diabetes (non-parametric comparison of medians at end of study 22.0% binding [unadjusted 95% CI 19.5, 24.5]) and the lowest responses were observed in non-insulin-using patients with type 2 diabetes in which there was no difference in medians values at end of study. There were no correlations between antibody binding and glycemic control (measured using HbA1c), insulin dose requirements, hypoglycemic events, or pulmonary function (measured by changes in forced expiratory volume in one second [FEV1] and diffusion capacity of carbon monoxide [DLco]). Antibody responses were IgG in type. Differences in antibody levels observed in patients with type 1 vs. type 2 diabetes were maintained over the 24-month extension trials. Peak antibody levels across all groups were generally observed after 6-12 months of insulin therapy. Inhaled insulin therapy was not associated with a greater incidence of allergy or other hypersensitivity reactions.
Conclusion
Inhaled insulin was observed to produce a larger antibody response than sc insulin. Insulin antibody binding has not been associated with adverse clinical consequences in trials to date.
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