Inhaled insulin in diabetes management: a review of efficacy, safety, and patient-centered outcomes

Authors

  • Alwin Raj Department of Pharmacology, Azeezia Institute of Medical Sciences and Research, Kollam, Kerala, India
  • Shruti Deshpande Department of Medical Affairs, IntelliMed Healthcare Solutions, Mumbai, Maharashtra, India
  • Rashmi Hegde IntelliMed Healthcare Solutions, Mumbai, Maharashtra, India
  • Anish Desai Department of Medical Affairs, IntelliMed Healthcare Solutions, Mumbai, Maharashtra, India
  • Sunaina Anand Department of Medical Affairs, IntelliMed Healthcare Solutions, Mumbai, Maharashtra, India

DOI:

https://doi.org/10.18203/2320-6012.ijrms20252819

Keywords:

Inhaled insulin, Technosphere insulin, Afrezza, Diabetes management, Pulmonary delivery, Glycaemic control, , Ultra-rapid insulin

Abstract

Inhaled insulin offers a non-invasive alternative to subcutaneous insulin for managing diabetes mellitus. Technosphere insulin (TI), marketed as Afrezza, delivers ultra-rapid-acting insulin via the pulmonary route, facilitating rapid absorption and improved post-prandial glucose (PPG) control. Clinical trials have demonstrated that TI achieves non-inferior glycaemic control compared to subcutaneous rapid-acting insulins in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), with notable reductions in HbA1c and enhanced PPG outcomes. TI’s fast onset (peak concentration ~15 minutes) and short duration reduce late hypoglycaemia risk. Studies also report improved patient satisfaction due to greater ease of use and reduced injection burden, supporting better treatment adherence. The most common adverse effect is mild, transient cough; small reversible declines in pulmonary function (FEV1) have been observed, necessitating careful patient selection and monitoring. Inhaled insulin is contraindicated in individuals with chronic lung diseases or recent smoking history. Future research should explore its use in paediatric and pregnant populations and assess long-term safety, adherence, and cost-effectiveness. With expanding evidence from trials like INHALE-3, inhaled insulin represents a valuable addition to the diabetes treatment landscape, particularly for patients seeking flexible and patient-centred insulin therapy.

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References

American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2023;47(1):S20-42.

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. DOI: https://doi.org/10.1016/j.diabres.2019.107843

Hirsch IB, Juneja R, Beals JM, Antalis CJ, Wright EE. The Evolution of Insulin and How it Informs Therapy and Treatment Choices. Endocr Rev. 2020;41(5):733-55. DOI: https://doi.org/10.1210/endrev/bnaa015

Sims EK, Carr ALJ, Oram RA, DiMeglio LA, Evans-Molina C. 100 years of insulin: celebrating the past, present and future of diabetes therapy. Nat Med. 2021;27(7):1154-64. DOI: https://doi.org/10.1038/s41591-021-01418-2

Sousa F, Castro P, Fonte P, Sarmento B. How to overcome the limitations of current insulin administration with new non-invasive delivery systems. Ther Deliv. 2015;6(1):83-94. DOI: https://doi.org/10.4155/tde.14.82

Brixner D, Edelman SV, Sieradzan R, Gavin JR. Addressing the Burden of Multiple Daily Insulin Injections in Type 2 Diabetes with Insulin Pump Technology: A Narrative Review. Diabetes Ther. 2024;15(7):1525-34. DOI: https://doi.org/10.1007/s13300-024-01598-3

El Maalouf IR, Capoccia K, Priefer R. Non-invasive ways of administering insulin. Diabetes Metab Syndr 2022;16(4):102478. DOI: https://doi.org/10.1016/j.dsx.2022.102478

Mathieu C, Gale EAM. Inhaled insulin: gone with the wind? Diabetologia. 2008;51(1):1-5. DOI: https://doi.org/10.1007/s00125-007-0875-x

Fleming LW, Fleming JW, Davis CS. Afrezza: An inhaled approach to insulin delivery. J Am Assoc Nurse Pract. 2015;27(10):597-601. DOI: https://doi.org/10.1002/2327-6924.12247

Klonoff DC. Afrezza inhaled insulin: the fastest-acting FDA-approved insulin on the market has favorable properties. J Diabetes Sci Technol. 2014;8(6):1071-3. DOI: https://doi.org/10.1177/1932296814555820

American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1):S181-206. DOI: https://doi.org/10.2337/dc25-S009

Heinemann L, Baughman R, Boss A, Hompesch M. Pharmacokinetic and Pharmacodynamic Properties of a Novel Inhaled Insulin. J Diabetes Sci Technol. 2017;11(1):148-56. DOI: https://doi.org/10.1177/1932296816658055

Rave K, Potocka E, Heinemann L, Heise T, Boss AH, Marino M, et al. Pharmacokinetics and linear exposure of AFRESA compared with the subcutaneous injection of regular human insulin. Diabetes Obes Metab. 2009;11(7):715-20. DOI: https://doi.org/10.1111/j.1463-1326.2009.01039.x

Nuffer W, Trujillo JM, Ellis SL. Technosphere insulin (Afrezza): a new, inhaled prandial insulin. Ann Pharmacother. 2015;49(1):99-106. DOI: https://doi.org/10.1177/1060028014554648

Rave K, Heise T, Heinemann L, Boss AH. Inhaled Technosphere insulin in comparison to subcutaneous regular human insulin: time action profile and variability in subjects with type 2 diabetes. J Diabetes Sci Technol. 2008;2(2):205-12. DOI: https://doi.org/10.1177/193229680800200206

Levin P, Hoogwerf BJ, Snell-Bergeon J, Vigers T, Pyle L, Bromberger L. Ultra Rapid-Acting Inhaled Insulin Improves Glucose Control in Patients With Type 2 Diabetes Mellitus. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol. 2021;27(5):449-54. DOI: https://doi.org/10.1016/j.eprac.2020.10.004

Bode BW, McGill JB, Lorber DL, Gross JL, Chang PC, Bregman DB, et al. Inhaled Technosphere Insulin Compared with Injected Prandial Insulin in Type 1 Diabetes: A Randomized 24-Week Trial. Diabetes Care. 2015;38(12):2266-73. DOI: https://doi.org/10.2337/dc15-0075

Hirsch IB, Beck RW, Marak MC, Kudva Y, Akturk HK, Bhargava A, et al. A Randomized Trial Comparing Inhaled Insulin Plus Basal Insulin Versus Usual Care in Adults With Type 1 Diabetes. Diabetes Care. 2025;48(3):353-60. DOI: https://doi.org/10.2337/dc24-1832

Hirsch IB, Beck RW, Marak MC, Calhoun P, Mottalib A, Salhin A, et al. A Randomized Comparison of Postprandial Glucose Excursion Using Inhaled Insulin Versus Rapid-Acting Analog Insulin in Adults With Type 1 Diabetes Using Multiple Daily Injections of Insulin or Automated Insulin Delivery. Diabetes Care. 2024;47(9):1682-7. DOI: https://doi.org/10.2337/dc24-0838

Grant M, Heise T, Baughman R. Comparison of Pharmacokinetics and Pharmacodynamics of Inhaled Technosphere Insulin and Subcutaneous Insulin Lispro in the Treatment of Type 1 Diabetes Mellitus. Clin Pharmacokinet. 2022;61(3):413-22. DOI: https://doi.org/10.1007/s40262-021-01084-0

Hoogwerf BJ, Pantalone KM, Basina M, Jones MC, Grant M, Kendall DM. Results Of A 24-Week Trial Of Technosphere Insulin Versus Insulin Aspart In Type 2 Diabetes. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol. 2021;27(1):38-43. DOI: https://doi.org/10.1016/j.eprac.2020.11.002

Seaquist ER, Blonde L, McGill JB, Heller SR, Kendall DM, Bumpass JB, et al. Hypoglycaemia is reduced with use of inhaled Technosphere® Insulin relative to insulin aspart in type 1 diabetes mellitus. Diabet Med J Br Diabet Assoc. 2020;37(5):752-9. DOI: https://doi.org/10.1111/dme.14202

McGill JB, Weiss D, Grant M, Jones MC, Kendall DM, Hoogwerf BJ. Understanding inhaled Technosphere Insulin: Results of an early randomized trial in type 1 diabetes mellitus. J Diabetes. 2021;13(2):164-72. DOI: https://doi.org/10.1111/1753-0407.13099

Rüppel D, Dahmen R, Boss A, Jäger R, Grant M, Baughman R, et al. A Population Dose-Response Model for Inhaled Technosphere Insulin Administered to Healthy Subjects. CPT Pharmacomet Syst Pharmacol 2017;6(6):365-72. DOI: https://doi.org/10.1002/psp4.12189

Raskin P, Heller S, Honka M, Chang PC, Boss AH, Richardson PC, et al. Pulmonary function over 2 years in diabetic patients treated with prandial inhaled Technosphere Insulin or usual antidiabetes treatment: a randomized trial. Diabetes Obes Metab. 2012;14(2):163-73. DOI: https://doi.org/10.1111/j.1463-1326.2011.01500.x

Pittas AG, Westcott GP, Balk EM. Efficacy, safety, and patient acceptability of Technosphere inhaled insulin for people with diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2015;3(11):886-94. DOI: https://doi.org/10.1016/S2213-8587(15)00280-6

Gerber RA, Cappelleri JC, Kourides IA, Gelfand RA. Treatment satisfaction with inhaled insulin in patients with type 1 diabetes: a randomized controlled trial. Diabetes Care. 2001;24(9):1556-9. DOI: https://doi.org/10.2337/diacare.24.9.1556

McGill JB, Ahn D, Edelman SV, Kilpatrick CR, Santos Cavaiola T. Making Insulin Accessible: Does Inhaled Insulin Fill an Unmet Need? Adv Ther. 2016;33(8):1267-78. DOI: https://doi.org/10.1007/s12325-016-0370-1

González Sarmiento E. Inhaled insulin and its effects on the lungs. Arch Bronconeumol. 2007;43(12):643-5. DOI: https://doi.org/10.1016/S1579-2129(07)60148-7

Goldberg T, Wong E. Afrezza (Insulin Human) Inhalation Powder: A New Inhaled Insulin for the Management of Type-1 or Type-2 Diabetes Mellitus. P T Peer-Rev J Formul Manag. 2015;40(11):735-41.

Study Shows Promising Results for Inhaled Insulin as Treatment for Type 1 Diabetes. American Diabetes Association. Available at: https://diabetes.org/newsroom/press-releases/study-shows-promising-results-inhaled-insulin-treatment-type-1-diabetes. Accessed on 15 April 2025.

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Published

2025-08-29

How to Cite

Raj, A., Deshpande, S., Hegde, R., Desai, A., & Anand, S. (2025). Inhaled insulin in diabetes management: a review of efficacy, safety, and patient-centered outcomes. International Journal of Research in Medical Sciences, 13(9), 3908–3914. https://doi.org/10.18203/2320-6012.ijrms20252819

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Review Articles