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Randomized Controlled Trial
. 2026 Jan 1;49(1):179-187.
doi: 10.2337/dc25-1994.

INHALE-1: A Multicenter Randomized Trial of Inhaled Technosphere Insulin in Children With Type 1 Diabetes

Michael J Haller  1 , Lauren Kanapka  2 , Roshanak Monzavi  3 , Thomas J Mouse  2 , Gnanagurudasan Prakasam  4 , Asheesh K Dewan  5 , Linda A DiMeglio  6 , Lori M Laffel  7 , Steven M Willi  8 , Michael J Tansey  9 , Bryce A Nelson  10 , Himala Kashmiri  11 , Jamie R Wood  12 , Kashif Latif  13 , Perrin White  14 , Mark Kipnes  15 , Henry Rodriguez  16 , Joshua Smith  17 , David P Sparling  18 , Faisal S Malik  19 , Anna Cymbaluk  20 , Anuj Bhargava  21 , Laya Ekhlaspour  22 , Shannon Beasley  23 , Kristina Cossen  24 , Kupper A Wintergerst  25 , Rosanna Fiallo-Scharer  26 , David M Maahs  27 , Kathleen E Bethin  28 , Michael A Wood  29 , Patrick C Hanley  30 , Surya N Mulukutla  31 , Michelle Van Name  32 , Scott M Blackman  33 , Mary Pat Gallagher  34 , Mark A Clements  35 , Nicole Sheanon  36 , Konda Reddy  37 , Barry J Reiner  38 , Robin Gal  2 , Roy W Beck  2 ; INHALE-1 Study Group*
Collaborators, Affiliations
Randomized Controlled Trial

INHALE-1: A Multicenter Randomized Trial of Inhaled Technosphere Insulin in Children With Type 1 Diabetes

Michael J Haller et al. Diabetes Care. .

Abstract

Objective: To evaluate inhaled technosphere insulin (TI) in children with diabetes.

Research design and methods: A total of 230 youth 4-17 years old with type 1 (98%) or type 2 (2%) diabetes treated with multiple daily injections of insulin were randomly assigned 1:1 to TI or rapid-acting analog (RAA) insulin plus continuation of long-acting basal insulin and continuous glucose monitoring (CGM) for 26 weeks. The primary outcome was change in HbA1c, tested for noninferiority with margin of 0.4%.

Results: In intent-to-treat analysis, mean HbA1c (% ± SD) was 8.22 ± 0.87 at baseline and 8.41 ± 1.38 at 26 weeks with TI and 8.21 ± 0.96 and 8.21 ± 1.10, respectively, with RAA (adjusted difference = 0.18; 95% CI -0.07, 0.43; noninferiority P = 0.091). CGM-measured time in range 70-180 mg/dL was not significantly different between groups (adjusted difference -2.2%; 95% CI -7.0, 2.7; P = 0.38). Two severe hypoglycemic events occurred in the TI group and one in the RAA group. Change in forced expiration volume in 1 s from baseline to 26 weeks did not differ comparing TI and RAA (P = 0.53). The TI group reported greater treatment satisfaction (P = 0.004) and had less gain in weight and BMI percentile (P = 0.009) than did the RAA group.

Conclusions: The primary analysis did not meet the prespecified criteria for HbA1c noninferiority. However, TI use was safe over 26 weeks without affecting pulmonary function and was associated with greater treatment satisfaction and less weight gain compared with RAA, supporting TI as a treatment option for some pediatric patients with type 1 diabetes.

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Conflict of interest statement

Author Disclosures

M.J.H. reports receiving consultancy fees and serving as a scientific advisory board member for MannKind and SAB BIO, and consultancy fees from Sanofi. G.P. reports receiving consultancy fees and reports serving as a principal investigator in MannKind-funded research. L.A.D. reports research support to her institution from Lilly, Sanofi, and Zealand and consulting fees from Tandem Diabetes. L.M.L. reports consultant and advisory Board fees from Boehringer Ingelheim, Janssen, Dexcom, Medtronic, Sequel, Tandem Diabetes, Sanofi, MannKind, Arbor Biotech, Vertex. S.M.W. reports receiving advisory board fees from Bohringer-Ingelheim and Mannkind. B.A.N. reports receiving advisory board fees from Sanofi. J.R.W. reports receiving research funding from Insulet and Medtronic. K.L. reports receiving advisory board fees from Mannkind. M.K. reports receiving research grants from 89bio, Medtronic, Abbott, Akero Therapeutics, Biomea Fusion, Carmot, Dexcom, AbbVie, Amgen, Biolinq, Diamyd, Endogenex, Insulet, IONIS Pharmaceuticals, Kowa, Novo Nordisk, Tandem, Zucara Therapeutics, Zydus, Sinocare, Boehringer Ingelheim, Corcept, and Eli Lilly; and advisory board fees from AP stem and Corcept. H.R. reports receiving advisory board fees from Mannkind. A.B. reports receiving research support from Verdiva Bio, Amgen Inc, Endogenix, Gasherbrum Bio, VtV Therapeutics, Boehringer Ingelheim Pharmaceuticals, Abbott Diabetes Care, AbbVie, Covance, Dexcom, Eli Lilly, Madrigal Pharmaceuticals, Medtronic, Novo Nordisk, MannKind, Carmot, Quintiles, Akero, 89bio, Viking Therapeutics, PPD, and Zydus. L.E. receives salary support from the National Institute of Diabetes and Digestive and Kidney Diseases, served on the advisory boards of Abbott, Diabetes Center Berne, Sequel, MannKind, and Medtronic; reports receiving consulting fees from Jaeb and Tandem Diabetes Care; and has received honorarium fees from Med Learning Group (Sanofi-sponsored grant), Tandem Diabetes Care, Medtronic, and Insulet. L.E.’s institution has received research support from Breakthrough T1D, Medtronic, Mannkind, and Abbott. D.M.M. reports research support from the National Institutes of Health, National Science Foundation, Breakthrough T1D, and the Helmsley Charitable Trust; and has consulted for Abbott, Sanofi, Eli Lilly, Medtronic, Biospex, Kriya, and Enable Biosciences. D.M.M. reports that his institution has received research support from Dexcom. M.A.W. reports receiving speaker fees from Alexion, Sanofi, and Mannkind. M.V.N. reports receiving consultancy fees from Soleno therapeutics and Novo Nordisk, and that her institution has received research funding or support on her behalf from Provention Bio and Novo Nordisk. S.M.B. reports receiving grants paid to their institution by the Cystic Fibrosis Foundation, Jaeb Center for Health Research, and MannKind, and reports study support to their institution from Dexcom. M.A.C. reports receiving research support from Dexcom and Abbot, and consultancy fees from Glooko. R.W.B. reports his institution has received funding on his behalf as follows: grant funding, study supplies, and consulting fees from Insulet, Tandem Diabetes Care, and Beta Bionics; grant funding and study supplies from Dexcom and Abbott; grant funding from Bigfoot Biomedical, embecta, Sequel Med Tech, and MannKind; study supplies from Medtronic; consulting fees and study supplies from Novo Nordisk; consulting fees from Vertex, Hagar, DreaMed, Ypsomed, Abata Therapeutics, Eli Lilly and Zucara. No other potential conflicts of interest relevant to this article were reported.

Figures

Fig. 1
Fig. 1. CGM Measured Mean Glucose by Hour at 26 Weeks.
The circles denote the median values and the lower and upper boundaries of the shaded region represent the 25th and 75th percentiles, respectively.
See this image and copyright information in PMC

References

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