Dissociation of Lung Function Changes with Humoral Immunity during Inhaled Human Insulin Therapy

Teeter, John G.; Riese, Richard J.

doi:10.1164/rccm.200512-1861oc

Cited by 40 publications

(41 citation statements)

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“…Consistent with previously published short-term data (11)(12)(13)(14), the present study demonstrates that EXU therapy is equally as effective in maintaining glycemic control as SC insulin while generally having a similar safety profile and minimal impact on lung function.…”

Section: ])supporting

confidence: 91%

“…By using nonstandardized lung function testing, trials of EXU in adult type 1 diabetic patients identified small treatment group differences in lung function over 6 months, favoring SC insulin (12,13). A subsequent short-term (3-month) study in type 1 diabetic patients using standardized methodology showed that these differences occurred early and were not progressive after 2-4 weeks, were clinically insignificant, and resolved within 2 weeks of discontinuation of treatment (14).…”

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confidence: 99%

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Two-Year Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 1 Diabetes

et al. 2007

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OBJECTIVE -The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. , indicating that the significant difference between the treatment groups in FEV 1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1%) that decreased to 1.3% by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 Ϯ 0.07% [0.13-0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with SC insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0. RESEARCH DESIGN AND METHODS

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Section: ])supporting

confidence: 91%

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confidence: 99%

Two-Year Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 1 Diabetes

et al. 2007

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“…[13][14][15][16][17][18] The magnitude of reduction in FEV1 was similar in both type 1 and type 2 diabetes patients.…”

Section: Forced Expiratory Volume In 1 Secondmentioning

confidence: 80%

“…Moreover, differences in FEV1 between the treatment groups resolved within two weeks of discontinuation of inhaled insulin. 15 Similarly, in a 24-week cross-over study, small reductions in baseline FEV1 were observed within two weeks of initiating inhaled insulin therapy and were reversible upon discontinuation of therapy. 18 The results of a longer-duration study of inhaled insulin in type 1 diabetes patients indicate that the initial reductions in FEV1 occurred within the first three months of therapy and were significantly different between treatment groups following one year of therapy (mean annual rates of decline in FEV1…”

Section: Forced Expiratory Volume In 1 Secondmentioning

confidence: 95%

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Inhaled Insulin in Clinical Practice A Focus on Pulmonary Safety

Camus¹

2007

US Endocrinology

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As inhaled insulin is a novel drug substance intended for chronic administration via a novel route, respiratory safety has been a cause of concern. Consequently, the respiratory safety of inhaled insulin has been studied extensively in both type 1 and type 2 diabetes populations. This brief review will examine the available safety data for inhaled insulin in terms of pulmonary function. The Inhaled Route of AdministrationThe pulmonary route has been the most widely researched non-invasive alternative to subcutaneous administration of polypeptides. It offers the greatest potential for systemic insulin delivery, since some of the features that make the lung so well suited for gas exchange-particularly its huge surface area-also make it an ideal organ for absorption of small molecules into the bloodstream. Human lungs have a large (greater than 100m 2 ), thin (0.1-0.2 micrometers), highly vascular epithelial surface area, permitting rapid passage of insulin from the alveoli into the systemic circulation.1 The lungs tolerate the administration of polypeptides immunologically and the distal airways lack significant muccocilliary transport, allowing time for absorption. The main disadvantage of inhaled drug delivery is the requirement for a specific particle size (1-3 micrometers) to achieve deep alveolar deposition. 2 Small peptides-such as insulin (approximately 6,000 daltons)-are readily absorbed, provided they are administered in the form of particles with the ideal particle size. Factors Affecting Inhaled Insulin Absorption Exposure to Tobacco SmokeThe use of inhaled insulin is contraindicated in patients who smoke. For safety purposes, patients must have stopped smoking more than six months earlier in order to be considered for treatment with Exubera. This is because the bioavailability of insulin is increased in chronic smokers compared with non-smokers, even some months after smoking cessation.Studies examining inhaled insulin absorption have shown that active smoking increases absorption of inhaled insulin two-to five-fold, which can expose the patient to the risk of hypoglycemia. However, the mechanism by which smoking affects inhaled insulin absorption is still unknown. This is a public health issue and young type 1 diabetics in particular should be told not to commence smoking if they want to benefit from therapy with Exubera. In contrast, the absorption of subcutaneous insulin is not affected by smoking.3,4The effect of passive smoking on the absorption of inhaled insulin has also been studied and-in contrast to the effects of active smoking-the investigators reported that that acute passive smoking caused a decrease in lung permeability, which in turn resulted in a decrease in inhaled insulin bioavailability. However, this did not create a risk for hypoglycemia. 5Likewise, smoking a single cigarette is associated with a decrease in insulin absorption. Lung DiseaseThe use of inhaled insulin is altered in patients with unstable or poorly controlled lung disease. Therefore, inhaled insulin is not recommende...

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The science behind Exubera^®

Schachner

2008

Drug Development Research

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Fear of needles constitutes a significant barrier to the use of insulin. Lung tissue offers a large permeable surface for rapid and predictable absorption of insulin into the bloodstream. Exubera insulin was the first inhaled insulin to be approved and marketed for clinical use. The present review is intended to summarize the data to present with Exubera insulin. The pharmacodynamic effect of this inhaled insulin is similar to that of injected regular human insulin. There are small changes in lung function that parallel age-related changes in patients who are not taking inhaled insulin. Cough occurs frequently but does not affect the overall insulin effect. Patients who start using insulin gain weight, but there is less weight gain with Exubera use than with comparable doses of injected insulin. In multiple studies, the incidence of hypoglycemia with Exubera is similar to that with regular insulin. There is concern that insulin may act as a growth factor on the lung epithelium. Recently, analysis of existing data showed that six patients on Exubera developed lung cancer compared to only one on comparator injectable insulin, all cases occurred in former smokers. However, studies were not powered for this safety issue and numbers were too small to conclude a causal relationship between Exubera exposure and occurrence of lung cancer. Pfizer decided to discontinue marketing Exubera on October 18, 2007. The decision was based upon failure to meet financial landmarks rather than due to concern about possible safety issues. Drug Dev Res 69: 130-137, 2008.

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Dissociation of Lung Function Changes with Humoral Immunity during Inhaled Human Insulin Therapy

Abstract: The small lung function changes observed with INH therapy are not mediated by the humoral immune response, or associated with acute decrements in lung function immediately after insulin inhalation.

Cited by 40 publications

References 27 publications

Two-Year Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 1 Diabetes

Two-Year Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 1 Diabetes

Inhaled Insulin in Clinical Practice A Focus on Pulmonary Safety

The science behind Exubera^®

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Dissociation of Lung Function Changes with Humoral Immunity during Inhaled Human Insulin Therapy

Abstract: The small lung function changes observed with INH therapy are not mediated by the humoral immune response, or associated with acute decrements in lung function immediately after insulin inhalation.

Cited by 40 publications

References 27 publications

Two-Year Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 1 Diabetes

Two-Year Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 1 Diabetes

Inhaled Insulin in Clinical Practice A Focus on Pulmonary Safety

The science behind Exubera®

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Product

Resources

About

The science behind Exubera^®