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

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 HbA_1c, tested for noninferiority with margin of 0.4%. RESULTS In intent-to-treat analysis, mean HbA_1c (% ± 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 HbA_1c 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.