Comparison of pharmacokinetics and pharmacodynamics of inhaled technosphere insulin and subcutaneous insulin lispro in the treatment of type 1 diabetes mellitus
Open accessAbstract
BACKGROUND: Insulin (TI; MannKind Corporation, Westlake Village, CA, USA) and subcutaneous insulin lispro (LIS) across a wide range of doses. OBJECTIVES: This single-center, open-label, randomized, cross-over study defined the pharmacokinetic/pharmacodynamic curves for inhaled TI vs subcutaneous LIS in persons with type 1 diabetes mellitus. METHODS: Each volunteer received six treatments while undergoing euglycemic clamps: three doses of TI (10, 30 and 120 U) and LIS (8, 30, and 90 U). Primary endpoint was area under the glucose infusion rate vs time curve from start of treatment administration to end of clamp. Key secondary endpoints included readouts of insulin exposure and timing of pharmacokinetic/pharmacodynamic profiles. RESULTS: for TI. Time to reach 10% of the maximum glucose infusion rate was 7 to 15 min for TI vs 21 to 38 min for LIS. End of effect was dose dependent for both treatments, ranging from 2 to 6 h (TI) and 5 to 10 h (LIS). Glucose infusion rate exhibited saturation for both treatments. Technosphere Insulin produced a lesser total effect per unit insulin than LIS due to its faster absorption and correspondingly shorter duration of exposure. The difference was large enough to require significantly different doses to achieve the same total effect. CONCLUSIONS: Technosphere Insulin has a considerably faster onset and shorter duration of action than LIS. Consequently, the overall effect of TI is smaller than that of LIS and unit-for-unit dose conversion is not appropriate. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02470637; 12 June, 2015.
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Afrezza is the fastest-acting exogenous insulin due to rapid absorption from the lungs, and eliminates the delays seen with subcutaneous injection.
“Afrezza (MannKind, Danbury, CT, USA), a human insulin inhaled powder, is the fastestacting exogenous insulin due to rapid absorption from the lungs, and eliminates the delays seen with subcutaneous injection.84”
From The future of type 1 diabetes therapy (2025) · cites this paper as [84]
The Conclusions (page unavailable) say inhaled Technosphere Insulin, sold as Afrezza, has a faster onset than subcutaneous lispro. But they place its time-action profile between IV bolus and subcutaneous insulin; the Introduction reports IV insulin reaching peak concentration sooner. The claim that Afrezza is the fastest-acting exogenous insulin and eliminates injection-related delays therefore overstates the paper's findings. (LLM, conf=0.89)
Experimental — accuracy not yet measuredInhaled insulin has faster onset and shorter duration compared with the rapid-acting insulin analog lispro.
“Studies comparing inhaled insulin with injectable insulin have demonstrated its faster onset and shorter duration compared with the RAA insulin lispro as well as clinically meaningful A1C reductions and weight reductions compared with the RAA insulin aspart over 24 weeks (186-188).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [188]
Inhaled insulin produces clinically meaningful A1C reductions compared with insulin aspart over 24 weeks.
“Studies comparing inhaled insulin with injectable insulin have demonstrated its faster onset and shorter duration compared with the RAA insulin lispro as well as clinically meaningful A1C reductions and weight reductions compared with the RAA insulin aspart over 24 weeks (186-188).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [188]
The Results (Patient Demographics; page unavailable) report baseline glycated hemoglobin, not a change in A1C. The Discussion (Clinical Use; page unavailable) discusses glucose control compared with insulin aspart, and the References list a 24-week trial, but our copy does not report whether inhaled insulin produced clinically meaningful A1C reductions over 24 weeks. (LLM, conf=0.74)
Experimental — accuracy not yet measuredInhaled insulin produces weight reductions compared with insulin aspart over 24 weeks.
“Studies comparing inhaled insulin with injectable insulin have demonstrated its faster onset and shorter duration compared with the RAA insulin lispro as well as clinically meaningful A1C reductions and weight reductions compared with the RAA insulin aspart over 24 weeks (186-188).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [188]
The Discussion > Clinical Use compares inhaled insulin with insulin aspart for time in glucose range and hypoglycemia, but does not report weight changes. The References list a 24-week inhaled-insulin trial; our copy does not state whether that trial found weight reductions compared with aspart. Searched for weight reduction, insulin aspart, and 24-week outcomes. (LLM, conf=0.74)
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Research works printed but not linked: 18
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ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s009 · Cited by 851 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s009 · Cited by 728 · see citing works
The future of type 1 diabetes therapy
Ziegler, A.-G., Cengiz, E., & Kay, T. W. H. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01438-2 · Cited by 42 · see citing works
Time–Action Profile of Technosphere Insulin in Children with Type 1 Diabetes
Haller, M. J., Jones, M. C., Bhavsar, S., & Kaiserman, K. B. (2023) · Diabetes Therapy · doi:10.1007/s13300-023-01368-7 · Cited by 16 · see citing works
- Authors
- Grant, M., Heise, T., & Baughman, R.
- Affiliations
- MannKind Corporation (United States) (US)
- Profil Institute for Metabolic Research (DE)
- Corresponding author
- Grant, Marshall
- Venue
- Clinical Pharmacokinetics
- Published
- 2021-11-13
- Volume
- 61
- Issue
- 3
- Pages
- 413-422
- ISSN
- 0312-5963 (ISSN-L)
- 1179-1926
- PMC
- PMC8891188
- OpenAlex
- W3213041209
- Cited by
- 30
- References
- 0
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 4 · 2023: 3 · 2022: 2
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Pharmacokinetics (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- mannkind corporation
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- inhaled insulin, Technosphere insulin, insulin lispro, type 1 diabetes, pharmacokinetics, pharmacodynamics, glucose infusion rate, euglycemic clamp, onset of action, duration of action, dose conversion, insulin absorption
- MeSH terms
- Blood Glucose, Diabetes Mellitus, Type 1, Glucose, Humans, Hypoglycemic Agents, Insulin, Cross-Over Studies, Insulin Lispro
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