Safety of intranasal human insulin: A review
Abstract
Aims: To conduct a review in order to assess the safety of intranasal human insulin in clinical studies as well as the temporal stability of nasal insulin sprays. Material and methods: An electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were extracted. Results: A total of 38 studies in 1092 individuals receiving acute human intranasal insulin treatment and 18 studies in 832 individuals receiving human intranasal insulin treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycaemia or severe adverse events (AEs) were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other AEs were less commonly reported. There were no reports of participants being excluded as a result of AEs. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks showed that it had a chemical stability of up to 57 days. Conclusions: Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns; however, there were insufficient data to ensure the long‐term safety of this method of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment.
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The used dose of 160 U resulted in substantial effects on brain activity, comparable to oral glucose ingestion, and has been widely used in previous trials on acute brain effects of insulin.
“Despite the lack of data on the exact amount of insulin reaching the brain, previous trials found that the used dose of 160 U resulted in substantial effects on brain activity6,7, comparable to oral glucose ingestion, and this dose has been widely used in previous trials on acute brain effects of insulin38.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [38]
Irritation of the nasal mucosa is the most commonly reported side effect of IN insulin, and the IN route for insulin delivery is safe and well-tolerated during acute and chronic use.
“It was concluded that irritation of the nasal mucosa is the most commonly reported side effect of IN insulin and that the IN route for insulin delivery is safe and well-tolerated both during acute and chronic use.”
From Intranasal insulin (2021) · cites this paper as [51]
Eighteen studies used chronic IN insulin administration with daily doses between 20 and 160 IU, or 0.5 and 1.5 U kg-1 body weight, for 21 days to 9.7 years, with 832 participants.
“Eighteen studies used chronic administration with daily doses of between 20 and 160 IU, or 0.5 and 1.5 U kg -1 body weight, for time periods between 21 days and 9.7 years with a combined number of 832 participants.”
From Intranasal insulin (2021) · cites this paper as [51]
Until 2 November 2017, 38 studies on acute IN insulin administration at doses between 10 and 160 IU and including 1092 participants did not yield adverse events or cases of hypoglycaemia.
“Until 2 November 2017, 38 studies on acute IN insulin administration at doses between 10 and 160 IU and including 1092 participants did not yield adverse events or cases of hypoglycaemia.”
From Intranasal insulin (2021) · cites this paper as [51]
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Self-citationInsulin modulates emotional behavior through a serotonin-dependent mechanism
Martin, H., Bullich, S., Martinat, M., Chataigner, M., Di Miceli, M., Simon, V., Clark, S., Butler, J., Schell, M., Chopra, S., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-022-01812-3 · Cited by 50 · see citing works
Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase
Hummel, J., Benkendorff, C., Fritsche, L., Prystupa, K., Vosseler, A., Gancheva, S., Trenkamp, S., Birkenfeld, A. L., Preissl, H., Roden, M., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00869-w · Cited by 48 · see citing works
Self-citationThe role of insulin sensitivity and intranasally applied insulin on olfactory perception
Edwin Thanarajah, S., Hoffstall, V., Rigoux, L., Hanssen, R., Brüning, J. C., & Tittgemeyer, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-43693-7 · Cited by 46 · see citing works
Insulin Action in the Hypothalamus Increases Second-Phase Insulin Secretion in Humans
Heni, M., Wagner, R., Willmann, C., Jaghutriz, B. A., Vosseler, A., Kübler, C., Hund, V., Scheffler, K., Peter, A., Häring, H.-U., et al. (2020) · Neuroendocrinology · doi:10.1159/000504551 · Cited by 36 · see citing works
Self-citationPlomgaard, P., Hansen, J. S., Ingerslev, B., Clemmesen, J. O., Secher, N. H., van Hall, G., Fritsche, A., Weigert, C., Lehmann, R., Häring, H., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13615 · Cited by 16 · see citing works
Self-citation
- Authors
- Schmid, V., Kullmann, S., Gfrörer, W., Hund, V., Hallschmid, M., Lipp, H., Häring, H., Preissl, H., Fritsche, A., & Heni, M.
- Affiliations
- German Center for Diabetes Research (DE)
- Universitätsklinikum Tübingen (DE)
- Helmholtz Munich (DE)
- Corresponding author
- Heni, Martin
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2018-04-06
- Volume
- 20
- Issue
- 7
- Pages
- 1563-1577
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2792857395
- Cited by
- 110
- References
- 77
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 13 · 2023: 10 · 2022: 16 · 2021: 18 · 2020: 17 · 2019: 11 · 2018: 3
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01GI0925)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- intranasal insulin, human insulin, drug safety, adverse events, hypoglycemia, nasal irritation, temporal stability, chemical stability, insulin delivery, long-term safety
- MeSH terms
- Administration, Intranasal, Aerosols, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Drug Compounding, Drug Stability, Humans, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Recombinant Proteins, Protein Stability, Insulin, Regular, Human
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