Innovations in diabetes medications and technologies have revolutionized our approach to the management of diabetes. Automated insulin delivery (AID) systems have substantially improved overall glycemia and time-in-range; however, AID systems do not eliminate postprandial hyperglycemia or correct hyperglycemia quickly, given the glucose-lowering action lag of insulins that are used in AID systems. Inhaled insulin offers a novel approach to prandial insulin delivery, characterized by rapid absorption kinetics and a “rapid on, rapid off” pharmacokinetic profile that closely mimics endogenous insulin secretion and can compensate for the glucose-lowering action delay of subcutaneous insulin delivery. While the integration of inhaled insulin with AID systems presents an opportunity to address the limitations of subcutaneous insulin formulations, challenges remain in harmonizing the pharmacokinetics of inhaled insulin with AID systems. This article reviews the current evidence supporting the potential role of concomitant use of TI with AID and gaps in our current knowledge that need to be filled with future studies.
FanW, DengC, XuR, et al.Efficacy and safety of automated insulin delivery systems in patients with type 1 diabetes mellitus: A systematic review and meta-analysis. Diabetes Metab J, 2025; 49(2):235–251; doi: 10.4093/dmj.2024.0130
2.
AkturkHK, BrownSA, BeckRW, et al.Registration and real-life studies on automated insulin delivery systems. J Diabetes Sci Technol, 2025; 19(4):924–936; doi: 10.1177/19322968251334993
3.
GeraS, IyerJ, MeighanS, et al.A review of real-world evidence about the use of automated insulin delivery systems in people with type 1 diabetes. Endocr Pract, 2025; 31(9):1150–1161; doi: 10.1016/j.eprac.2025.06.004
4.
KudvaYC, RaghinaruD, LumJW, et al.; 2IQP Study Group. A randomized trial of automated insulin delivery in type 2 diabetes. N Engl J Med, 2025; 392(18):1801–1812; doi: 10.1056/NEJMoa2415948
5.
PasquelFJ, DavisGM, HuffmanDM, et al.; Omnipod 5 SECURE-T2D Consortium. Automated insulin delivery in adults with type 2 diabetes: A nonrandomized clinical trial. JAMA Netw Open, 2025; 8(2):e2459348; doi: 10.1001/jamanetworkopen.2024.59348
6.
BorelAL, LablancheS, WaterlotC, et al.Closed-loop insulin therapy for people with type 2 diabetes treated with an insulin pump: A 12-week multicenter, open-label randomized, controlled, crossover trial. Diabetes Care, 2024; 47(10):1778–1786; doi: 10.2337/dc24-0623
7.
DalyAB, BoughtonCK, NwokoloM, et al.Fully automated closed-loop insulin delivery in adults with type 2 diabetes: An open-label, single-center, randomized crossover trial. Nat Med, 2023; 29(1):203–208; doi: 10.1038/s41591-022-02144-z
8.
DavisGM, PetersAL, BodeBW, et al.Safety and efficacy of the omnipod 5 automated insulin delivery system in adults with type 2 diabetes: From injections to hybrid closed-loop therapy. Diabetes Care, 2023; 46(4):742–750; doi: 10.2337/dc22-1915
9.
HeinemannL, BaughmanR, BossA, HompeschM. Pharmacokinetic and pharmacodynamic properties of a novel inhaled insulin. J Diabetes Sci Technol, 2017; 11(1):148–156; doi: 10.1177/1932296816658055
10.
HallerMJ, JonesMC, BhavsarS, KaisermanKB. Time-action profile of technosphere insulin in children with type 1 diabetes. Diabetes Ther, 2023; 14(3):611–617; doi: 10.1007/s13300-023-01368-7
11.
HirschIB, BeckRW, MarakMC, et al.; INHALE-3 Study Group. 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):1682–1687; doi: 10.2337/dc24-0838
12.
AkturkHK, Snell-BergeonJK, RewersA, et al.Improved postprandial glucose with inhaled technosphere insulin compared with insulin aspart in patients with type 1 diabetes on multiple daily injections: The STAT Study. Diabetes Technol Ther, 2018; 20(10):639–647; doi: 10.1089/dia.2018.0200
13.
SeaquistER, BlondeL, McGillJB, et al.Hypoglycaemia is reduced with use of inhaled Technosphere® Insulin relative to insulin aspart in type 1 diabetes mellitus. Diabet Med, 2020; 37(5):752–759; doi: 10.1111/dme.14202
14.
HoogwerfBJ, PantaloneKM, BasinaM, et al.Results of 24-week trial of technosphere insulin versus insulin Aspart in type 2 diabetes. Endocr Pract, 2021; 27(1):38–43; doi: 10.1016/j.eprac.2020.11.002
15.
BodeBW, McGillJB, LorberDL, et al.; Affinity 1 Study Group. Inhaled technosphere insulin compared with injected prandial insulin in type 1 diabetes: A randomized 24-week trial. Diabetes Care, 2015; 38(12):2266–2273; doi: 10.2337/dc15-0075
16.
PittasAG, WestcottGP, BalkEM. 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):886–894; doi: 10.1016/S2213-8587(15)00280-6
17.
SherrJL, HeinemannL, FlemingGA, et al.Automated insulin delivery: Benefits, challenges, and recommendations. A consensus report of the joint diabetes technology working group of the European Association for the study of diabetes and the American Diabetes Association. Diabetologia, 2023; 66(1):3–22; doi: 10.1007/s00125-022-05744-z
18.
SeniorP, HramiakI. Fast-acting insulin aspart and the need for new mealtime insulin analogues in adults with type 1 and type 2 diabetes: A canadian perspective. Can J Diabetes, 2019; 43(7):515–523; doi: 10.1016/j.jcjd.2019.01.004
19.
LeahyJJL, AleppoG, FonsecaVA, et al.Optimizing postprandial glucose management in adults with insulin-requiring diabetes: Report and recommendations. J Endocr Soc, 2019; 3(10):1942–1957; doi: 10.1210/js.2019-00222
20.
RaskinP, HellerS, HonkaM, 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):163–173; doi: 10.1111/j.1463-1326.2011.01500.x
RaveK, PotockaE, HeinemannL, et al.Pharmacokinetics and linear exposure of AFRESA compared with the subcutaneous injection of regular human insulin. Diabetes Obes Metab, 2009; 11(7):715–720; doi: 10.1111/j.1463-1326.2009.01039.x
24.
HeinzerlingL, RaileK, RochlitzH, et al.Insulin allergy: Clinical manifestations and management strategies. Allergy, 2008; 63(2):148–155; doi: 10.1111/j.1398-9995.2007.01567.x
25.
HirschIB, BeckRW, MarakMC, et al.; INHALE-3 Study Group. A randomized trial comparing inhaled insulin plus basal insulin versus usual care in adults with type 1 diabetes. Diabetes Care, 2025; 48(3):353–360; doi: 10.2337/dc24-1832
26.
HallerMJ, KanapkaL, MonzaviR, et al.INHALE-1: A multi-center randomized trial of inhaled Technosphere insulin in children with type 1 diabetes. Diabetes Care, 2026; 49(1):179–187; doi: 10.2337/dc25-1994
27.
ZisserH, DassauE, LeeJJ, et al.Clinical results of an automated artificial pancreas using technosphere inhaled insulin to mimic first-phase insulin secretion. J Diabetes Sci Technol, 2015; 9(3):564–572; doi: 10.1177/1932296815582061
28.
GalderisiA, CohenN, CalhounP, et al.Effect of afrezza on glucose dynamics during HCL treatment. Diabetes Care, 2020; 43(9):2146–2152; doi: 10.2337/dc20-0091
29.
JacobsonC, KaisermanKB, UlloaJ, et al.Safety and efficacy of inhaled Technosphere® Insulin in the postprandial period with modified initial dose conversion. Diabetes Ther, 2025; 16(8):1695–1705; doi: 10.1007/s13300-025-01760-5
30.
KaisermanKB, UlloaJ, PleitezJ, et al.Replacing or supplementing automated insulin delivery with inhaled insulin: A 90-day randomized controlled trial. J Diabetes Sci Technol, 2025; doi: 10.1177/19322968251388128
