INHALE-1: Afrezza Safe but Not Superior to Rapid-Acting Analogue in Children, With Roy Beck, MD, PhD

Although it failed to reach the prespecified criteria for HbA1c noninferiority, inhaled technosphere insulin (TI) was proven safe and associated with greater treatment satisfaction than rapid-acting analogue (RAA) insulin in the INHALE-1 study.1

These data were presented at the International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) in Barcelona, Spain, by Roy Beck, MD, PhD, founder of the aeb Center for Health Research and lead investigator on the study. HCPLive spoke with Beck to discuss the pulmonary safety findings from this phase 3 trial.

“It’s advisable to have pulmonary function tests, and it can be done in the office,” Beck told HCPLive. “Maybe 6 months after they’ve started treatment, and if they’re doing okay, then maybe after another 6 months. And then if they’re okay, maybe once a year, unless someone’s getting symptoms. But we did not identify any risk.”

INHALE-1 was a phase 3, open-label, randomized clinical trial evaluating TI’s efficacy and safety in combination with basal insulin versus RAA - including insulin lispro, insulin glulisine, and insulin aspart in combination with basal insulin – in pediatric patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). The trial included 26 weeks of randomized treatment with either TI or RAA, all patients entered an extension period of TI treatment until week 52.2

Patients were eligible for INHALE-1 if they were ≥4 and <18 years old with a clinical diagnosis of T1DM or T2DM and had been using insulin for ≥6 months for T1DM or ≥3 months for T2DM. Additionally, patients were required to have an HbA1c ≥7% and ≤11% and be receiving an average prandial dose of insulin ≥2 units per meal, among other criteria. Patients were excluded if they had a history of recent blood transfusions, asthma, serious complications of diabetes, or respiratory tract infection within 14 days of screening, among other criteria.2

Patients were then randomly assigned in a 1:1 ratio to either the TI or RAA group. Randomization was stratified by diabetes subtype, baseline HbA1c (<8.5% or ≥8.5%), and age (4 to <13 years or 13 to <18 years). Both groups continued using basal insulin, typically once daily in the evening with either insulin glargine, insulin degludec, or insulin detemir. The primary outcome was change in HbA1c by 26 weeks, with secondary outcomes including binary HbA1c metrics, CGM metrics, and others. Investigators also examined pulmonary function testing as a safety endpoint.1

A total of 313 participants were screened and 230 were randomized to the TI group (n = 117) or the RAA group (n = 113). Mean age was 12.6 years (standard deviation [SD], +/- 3 years). 225 patients presented with T1DM and 5 presented with T2DM. In intent-to-treat analysis, mean baseline HbA1c was 8.22 +/- 0.87 and 8.41 +/- 1.38 at 26 weeks with TI and 8.21 +/- 0.96 and 8.21 +/- 1.1, respectively, with RAA (adjusted difference, 0.18; 95% CI, -0.07 to 0.43; noninferiority P = .091).1

However, despite not meeting the prespecified criteria for HbA1c noninferiority, only 2 severe hypoglycemic events occurred in the TI group and 1 in the RAA group. Treatment was also shown to be safe without affecting pulmonary function compared with RAA, and the TI group reported greater treatment satisfaction (P = .004) and had less gain in weight and BMI percentile (P = .009) than the RAA group.1

“Both the parents and the children expressed greater satisfaction with treatment based on the specific validated survey that was used, even if they didn’t show a benefit in their glucose levels,” Beck said. “I think, possibly because of fewer injections, there’s a greater treatment satisfaction. We actually have a study that’s ongoing now that’s looking at whether starting pediatric patients newly diagnosed with type 1 diabetes on inhaled insulin rather than injections will benefit their adherence.”

Editors’ Note: Beck reports that his institution has received funding on his behalf from Insulet, Tandem Diabetes Care, Beta Bionics, Abbott, Dexcom, Sequel Med Tech, and others.

References

1. Haller MJ, Kanapka L, Monzavi R, et al. INHALE-1: A Multicenter Randomized Trial of Inhaled Technosphere Insulin in Children With Type 1 Diabetes. Diabetes Care. 2026;49(1):179-187. doi:10.2337/dc25-1994

2. MannKind Corporation. Afrezza INHALE-1 Study in Pediatrics (INHALE-1). ClinicalTrials.gov Identifier: NCT04974528. Updated May 6, 2025. Accessed April 17, 2026. https://clinicaltrials.gov/study/NCT04974528