INHALE-1: A Multicenter Randomized Trial of Inhaled Technosphere Insulin in Children With Type 1 Diabetes
Michael J. Haller, Lauren Kanapka, Roshanak Monzavi, Thomas J. Mouse, Gnanagurudasan Prakasam, Asheesh K. Dewan, Linda A. DiMeglio, Lori M. Laffel, Steven M. Willi, Michael Tansey, Bryce Nelson, Himala Kashmiri, Jamie Wood, Kashif Latif, Perrin C. White, Mark Kipnes, Henry Rodriguez, Joshua W. Smith, David P. Sparling, Faisal Malik, Anna Cymbaluk, Anuj Bhargava, Laya Ekhlaspour, Shannon Beasley, Kristina Cossen, Kupper A. Wintergerst, Rosanna Fiallo‐Scharer, David M. Maahs, Kathleen E. Bethin, Michael A. Wood, Patrick C. Hanley, Surya N. Mulukutla, Michelle Van Name, Scott M. Blackman, Mary Gallagher, Mark A. Clements, Nicole Sheanon, K. R. Reddy, Barry Reiner, Robin L. Gal, Roy W. Beck, INHALE-1 Study Group*, Lori M. Laffel, Elvira Isganaitis, Hannah Desrochers, Louise Ambler-Osborn, Jade Doolan, Kerry Milaszewski, David M. Maahs, Lisa Norlander, Priya Prahalad, Laya Ekhlaspour, S Shah, ILENIA BALISTRERI, Noor Alramahi, Eliana Frank, Nora Arrizon‐Ruiz, Michelle Van Name, Kate Weyman, Amy Steffen, Melinda Zgorski, Himala Kashmiri, Nikta Forghani, Heather Speer, Ana Cecília Ribeiro Cruz, Diana Martínez, Marissa Erickson, Hunter Vallejo, Perrin C. White, Jimmy Penn, Abha Choudhary, Colten Youngblood, Yazmin Molina, Michelle Murphy, Lisa Staples-Wherry, Chantal Nwosu, Michael Gottschalk, Anna Cymbaluk, Carla Demeterco‐Berggren, Ron S. Newfield, Marcela Vargas Trujillo, Jane J. Kim, Marla Hashiguchi, Maja Marinković, Mary Patterson, Michelle Rivera-Vega, Susan D. Phillips, Angela Y. Lam, Lisa Paglia, Shannan Davis, Kristina Cossen, Andrew Muir, Eric I. Felner, Lynette Gonzalez, Linton Cuff, Xiaomiao Lan‐Pidhainy, Amber Antich, Michael J. Haller, Laura M. Jacobsen, Brittany Bruggeman
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.