Published January 21, 2026 | Version v1
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INHALABLE INSULIN: A REVOLUTION IN DIABETES MANAGEMENT

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Considerable time and financial resources have been dedicated to the development of new medications that target various essential enzymes and signaling pathways, which have temporarily aided in mitigating this growing pandemic. Insulin continues to be regarded as the gold standard for treatment; however, it is frequently rejected by both patients and healthcare professionals (clinical inertia) due to the method of administration of this medication. Although ultra-short-acting insulin analogues assist in managing prandial glucose spikes, they necessitate 2-3 doses depending on meal intake. Furthermore, long-acting basal insulin is often needed to replicate normal physiological insulin baseline levels. This results in an average of 2-4 insulin injections per day, which many individuals find quite distressing. Patients frequently feel overwhelmed by the necessity of finger pricks for regular blood glucose monitoring, and the prospect of tracking blood glucose levels has often deterred a significant number of patients who guess their sugar levels before and after meals. Insulin therapy requires more stringent blood glucose monitoring, and in cases of hypoglycemic episodes or uncontrolled hyperglycemias, multiple finger pricks may be necessary. The discrepancies in blood glucose readings across various Point of Care (POC) glucometer devices do not alleviate the situation and only contribute to the existing frustration. Emphasizing alternative and innovative drug delivery methods for existing molecules can help shift the therapeutic paradigm towards more favorable outcomes. This article will explore one such transformative change in the drug delivery of insulin.

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Submitted
2026-01-21
According to the National Diabetes Statistics Report, 29.1 million people have diabetes mellitus (DM) in the U.S., or approximately 9.3% of the population. DM imposes a financial burden on both patients and the health care economy, with direct and indirect costs totaling $245 billion in 2012.1All patients with type-1 DM (T1DM) require insulin therapy. Patients with type-2 DM (T2DM) may also become dependent on exogenous insulin as their disease progresses. Approximately 6 million people in the U.S. require insulin therapy. Insulin therapy allows for better glycemic control, but patients are often hesitant to make the transition to insulin because of its adverse-event profile (e.g., hypoglycemia, weight gain) and because of fear of injections. Since injectable insulin was introduced into clinical practice in 1922, other routes of administration have been explored. Inhaled insulin, for example, offers the advantage of a larger area of absorption—approximately 70 to 140 square meters, or half of a tennis court. In 1924, the first study of inhaled insulin was conducted in human subjects at doses 30 times higher than that of the subcutaneous (SC) route of administration. In 2006, the Food and Drug Administration (FDA) approved the first inhaled insulin for patients with T1DM or T2DM. Exubera (Nektar Therapeutics/Pfizer) was derived from recombinant human insulin (rDNA origin), with a bioavailability of approximately 60%. It was available as a spray-dried insulin powder packaged in blisters containing 1 mg or 3 mg of insulin. Despite the promise of a new delivery system, Exubera did not find a profitable niche in the insulin market. Twenty-one months after its approval, the product was voluntarily withdrawn from the market because of low sales. The failure of Exubera may have resulted from several factors, including the high cost of the inhaler; dosing in milligrams, which may have confused patients who had been receiving conventional insulin therapy that was measured in units; the large size of the device; and an FDA warning regarding the potential for primary lung cancer.

References

  • [1]. World Health Organisation, Global Report on Diabetes. Geneva, 2016. Accessed on: 30 Aug 2016. [2].Turner R, Cull C, Holman R. United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996;124(1 Pt 2):136–45. doi: 10.7326/0003-4819-124-1_part_2-199601011-00011. [DOI] [PubMed] [Google Scholar] [3].Black C, Cummins E, Royle P, Philip S, Waugh N. The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation. Health Technol Assess. 2007;11(33):1–126. doi: 10.3310/hta11330. [DOI] [PubMed] [Google Scholar] [4]. FDA Approves First Ever Inhaled Insulin Combination Product for Treatment of Diabetes (Press release). Silver Spring, Maryland: FDA. 2006-01-27. [5]. John Simons (19 October 2007). "How the Exubera debacle hurts Pfizer". CNNMoney. Retrieved 2007-10-21. [6]. FDA News Release: FDA approves Afrezza to treat diabetes. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm403122.htm. [7]. Justin Gillis (January 28, 2006). "Inhaled Form of Insulin Is Approved". The Washington Post. Retrieved 2007-10-21. [8]. BBC Aug 4, 2006. Inhaled insulin given UK launch. [9].van Alfen-van der Velden AA, Noordam C, de Galan BE, Hoorweg-Nijman JJ, Voorhoeve PG, Westerlaken C. Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapy. Pediatr Diabetes. 2010;11(6):380–82. doi: 10.1111/j.1399-5448.2009.00597.x. [DOI] [PubMed] [Google Scholar] [10].From The Medical Letter on Drugs and Therapeutics. An Inhaled Insulin (Afrezza) JAMA. 2015;313(21):2176–217. doi: 10.1001/jama.2015.5634. [DOI] [PubMed] [Google Scholar] [11].Webster MW. Clinical practice and implications of recent diabetes trials. Curr Opin Cardiol. 2011;26(4):288–93. doi: 10.1097/HCO.0b013e328347b139. [DOI] [PubMed] [Google Scholar] [12]. Technosphere Insulin - How it works. MannKind Corp. 2007. Archived from the original on 2007-10-20. Retrieved 2007-10-22. [13].Ander H. Boss, Richard Petrucci, Daniel Lorber. Coverage of prandial insulin requirements by means of an ultra-rapid-acting inhaled insulin. J Diabetes Sci Technol. 2012;6(4):773–79. doi: 10.1177/193229681200600406. [DOI] [PMC free article] [PubMed] [Google Scholar] [14].Goldberg T, Wong E. Afrezza (Insulin Human) inhalational powder. A new inhaled insulin for the management of type-1 or type-2 diabetes mellitus. PT. 2015;40(11):735–41. [PMC free article] [PubMed] [Google Scholar] [15] Hussain A, Arnold JJ, Khan MA, Ahsan F. Absorption enhancers in pulmonary protein delivery. J Control Release 2004; 94: 15-24. [16] Song Y, Wang Y, Thakur R, Meidan VM, Michniak B. Mucosal drug delivery: Membranes methodologies, and applications. Crit Rev Ther Drug Carrier Syst 2004; 21: 195-256. [17] Cryan SA. Carrier-based strategies for targeting protein and peptide drugs to the lungs. AAPS J 2005; 7: E20-E41. [18] Owens DR. New horizons – Alternative routes for insulin delivery. Nat Rev Drug Discov 2002; 1: 529-540. 19. Wilde MI, McTavish D. Insulin lispro: A review of its pharmacological properties and therapeutic use in the management of diabetes mellitus. Drugs 1997; 54: 597-614. [20] Cefalu WT. Concept, strategies, and feasibility of non-invasive insulin delivery. Diabetes Care 2004; 27: 239-246. [21] Belmin J, Valensi P. Novel drug delivery systems for insulin. Clinical potential for use in the elderly. Drugs Aging 2003; 20: 303-312. [22] Laqueur E, Grevenstuk A. Uber die Wirkung intratrachealer Zuführung von Insulin. Klin Wochenschr 1924; 3: 1273-1274. [23] Heubner W, de Jongh SE, Laquer E. Uber Inhalation von Insulin. Klin Wochenschr 1924; 3: 2342-2343. 24. Gänsslen M. Uber Inhalation von Insulin. Klin Wochenschr 1925; 4: 71. 25. Wigley FW, Londono JH, Wood SH, Ship JC, Waldman RH. Insulin across respiratory mucosae by aerosol delivery. Diabetes 1971; 20: 552-556. 26. Elliott RB, Edgar BW, Pilcher CC, Quested C, McMaster J. Parenteral absorption of insulin from the lung in diabetic children. Aust Paediatr J 1987; 23: 293-297. 27. Kohler D, Schlüter KJ, Kerp L, Matthys H. Nicht radioaktives Verfahren zur Messung der Lungenpermeabilität. Inhalation von Insulin. Atemw-Lungenkrkh 1987; 13: 230-232.