Comprehensive Pulmonary Safety Review of Inhaled Technosphere® Insulin in Patients with Diabetes Mellitus
Open accessAbstract
BACKGROUND AND OBJECTIVE: ; MannKind Corporation, Westlake Village, CA, USA), is an ultra-rapid-acting inhaled insulin indicated to improve postprandial glycemic control in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Because TI is absorbed across the alveolar membrane, the objective of this analysis was to characterize its pulmonary safety. METHODS: Pooled data from 13 phase 2/3 clinical studies in 5505 patients with T1DM or T2DM treated with TI, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events (TEAEs), changes in pulmonary function, and lung malignancies. Radiographic changes in the lungs were monitored in a subset of 229 patients. RESULTS: Among 3017 patients receiving TI, the median duration of TI exposure was 168 days; median active-comparator and TP exposure durations were 363 and 149 days for 2198 and 290 patients, respectively. Respiratory TEAEs were comparable across treatments, except for a higher incidence of mild cough with TI in active-comparator studies (28.0% vs. 5.2%). Slight reversible declines in pulmonary function from baseline were observed for TI versus TP and active-comparator treatments, including in a subpopulation of patients with retrospectively identified lung dysfunction. Lung malignancies were reported in two patients on active TI therapy with a smoking history. No clinically significant changes from baseline were observed in radiographic images. CONCLUSIONS: Pulmonary safety assessment of the TI inhalation system did not identify any safety issues in individuals with either T1DM or T2DM.
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Inhaled insulin can cause cough or sore throat, and therapy must be monitored with periodic spirometry because of possible effects on lung function.
“Additionally, inhaled insulin can cause cough or sore throat, and therapy must be monitored with periodic spirometry because of possible effects on lung function (97).”
From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [97]
The Results (Respiratory Treatment-Emerent Adverse Events; page unavailable) identify cough as the most common respiratory adverse event with Technosphere insulin. The Discussion mentions throat irritation as an adverse effect of other inhaled medications, but does not establish sore throat as an effect of this insulin. The Methods (Pulmonary Safety; page unavailable) describe spirometry used in the studies, and the Results (Pulmonary Function; page unavailable) report small lung-function declines; neither passage says patients must undergo periodic spirometry during therapy. (LLM, conf=0.88)
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Research works printed but not linked: 21
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Holt, R. I. G., DeVries, J. H., Hess-Fischl, A., Hirsch, I. B., Kirkman, M. S., Klupa, T., Ludwig, B., Nørgaard, K., Pettus, J., Renard, E., et al. (2021) · Diabetes Care · doi:10.2337/dci21-0043 · Cited by 699 · see citing works
Self-citation
- Authors
- McGill, J. B., Peters, A., Buse, J. B., Steiner, S., Tran, T., Pompilio, F. M., & Kendall, D. M.
- Affiliations
- Washington University in St. Louis (US)
- University of Southern California (US)
- University of North Carolina at Chapel Hill (US)
- MannKind Corporation (United States) (US)
- Corresponding author
- Kendall, David M.
- Venue
- Clinical Drug Investigation
- Published
- 2020-07-27
- Volume
- 40
- Issue
- 10
- Pages
- 973-983
- ISSN
- 0114-2402 (ISSN-L)
- 1173-2563
- 1179-1918
- PMC
- PMC7511468
- OpenAlex
- W3044146994
- Cited by
- 35
- References
- 0
- Citations by year
- 2026: 15 · 2025: 6 · 2024: 6 · 2022: 1 · 2021: 7
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Drug Investigation (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- MannKind Corporation
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- inhaled insulin, Technosphere insulin, pulmonary safety, type 1 diabetes, type 2 diabetes, respiratory adverse events, lung function, lung malignancy, cough, pulmonary dysfunction
- MeSH terms
- Administration, Inhalation, Adult, Blood Glucose, Cough, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Insulin, Lung, Male, Middle Aged, Powders, Retrospective Studies, Postprandial Period
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