Objective
The INHALE-1st study will evaluate whether a differentiated mealtime insulin approach can reduce the day-to-day burden of care for youth newly-diagnosed with stage 3 type 1 diabetes (T1D) without compromising safety or glucose control. Standard care typically requires multiple daily mealtime injections plus a long-acting basal insulin, which can be especially challenging during the early “honeymoon” period when insulin needs change quickly. INHALE-1st will test Technosphere Insulin (TI; Afrezza), an ultra-rapid insulin taken by inhalation, paired with a once-daily basal insulin injection (TI-BI), as an alternative strategy in this early adjustment window.
The trial will enroll youth ages 10 to <18 years who start TI-BI within 10 days of diagnosis and continue for 13 weeks, with an optional extension of up to 26 additional weeks (for a potential total of 39 weeks). The study will assess effectiveness by measuring how consistently glucose levels stay within a target range (70-180 mg/dL) using continuous glucose monitoring (CGM) and by tracking HbA1c at scheduled visits. Safety will be monitored throughout, including lung function testing and evaluation of serious adverse events such as severe hypoglycemia and diabetic ketoacidosis (DKA). The study will also examine patient and parent experience through patient reported surveys (PROs) and various interviews to understand treatment satisfaction, usability, and whether reducing injections makes daily management feel more manageable. Results are intended to generate real world evidence to inform clinical practice and progress towards the broader goal of helping more patients.
Background Rationale
Type 1 diabetes (T1D) is one of the most common chronic conditions in children, affecting more than one million youth worldwide, with over 125,000 new cases diagnosed each year (Diabetes Atlas, 2025). A new diagnosis forces families to learn complex, high-stakes skills quickly: how to count carbohydrates, dose insulin, recognize low blood sugar, and respond to rapidly changing insulin needs. Standard therapy typically pairs a long-acting basal insulin with rapid-acting insulin injections at meals and for corrections. Although effective, this approach can be especially difficult in the first months after diagnosis, when insulin requirements fluctuate and daily life is already disrupted. Multiple daily injections, dosing and timing complexity, and needle anxiety can increase stress for both children and parents, highlighting the need for treatment options that reduce practical barriers without compromising safety or glucose control.
The INHALE-1st trial addresses this early adjustment period by evaluating Technosphere Insulin (TI; Afrezza), an ultra-rapid inhaled mealtime insulin, used together with basal insulin (BI). Afrezza is delivered through a breath-powered inhaler and acts quickly, which may help better match insulin action to the rise and fall of blood sugar after meals. Prior studies (Bode et al., 2015; Akturk et al., 2018) suggest that this profile can reduce post-meal glucose spikes, while pediatric research to date, including pharmacokinetic studies and prior trials, suggests acceptable safety and potential benefits such as less weight gain and greater treatment satisfaction (Haller et al., 2023). Previous sponsored pediatric studies, however, have only sampled youth already experienced with insulin therapy that switched to Afrezza from automated insulin delivery (AID) systems or multiple daily injections (MDI). The goal of the INHALE-1st study is to generate data that has the potential to position Afrezza as a first-insulin-therapy option for pediatrics, offering a treatment that may lessen the burden of diabetes management during youth and adolescents' critical growth phase.
By starting this approach soon after diagnosis, the study aims to determine whether inhaled insulin plus basal insulin can maintain strong glucose control while making day-to-day care easier for youth and families. Potential benefits include fewer injections, reduced needle anxiety, and mealtime dosing that fits more naturally into school, sports, and family routines. If successful, this regimen could help families feel more confident and engaged during the critical early months of T1D management, with implications for longer-term outcomes. Afrezza is already FDA-approved for adults, and pediatric labeling is currently under review by the FDA. Real world evidence from the INHALE-1st study is intended to further inform clinicians, patients, families, and regulators about Afrezza’s role in pediatric care.
Description of Project
Type 1 diabetes (T1D) is a chronic condition that often begins in childhood and requires lifelong insulin therapy to maintain glucose levels within a healthy range. For families, the early weeks after diagnosis can be overwhelming. Children must quickly adjust to frequent blood glucose checks or continuous glucose monitoring (CGM), along with multiple daily insulin injections, while parents navigate complex dosing schedules and monitoring techniques. These demands can create stress and impact adherence, making it harder to achieve optimal control during a critical period for establishing a foundation for children's long-term health.
The INHALE‑1st study is designed to explore a new approach that could ease this burden: inhaled insulin for newly-diagnosed pediatric patients. Afrezza® is an ultra‑rapid insulin delivered through a small, breath‑powered inhaler. Unlike traditional rapid‑acting insulin injections, Afrezza reaches the bloodstream rapidly and clears quickly, closely mimicking the body’s natural insulin response. This fast action may help reduce post‑meal blood sugar spikes and lower the risk of low blood sugar between meals. Just as importantly, inhaled insulin eliminates the need for multiple daily injections at mealtimes, which could make diabetes care less invasive and more manageable for children and families.
INHALE‑1st focuses on youth aged 10 to <18 years who have been recently (within 10 days) diagnosed with T1D. The study will evaluate whether a regimen combining inhaled insulin for meals with a once‑daily basal insulin injection is safe, effective, and practical in this population. Researchers will look at how well this approach helps participants maintain glucose levels in a healthy range, using continuous glucose monitoring (CGM) to capture real‑time data. They will also assess overall health markers to ensure Afrezza is well tolerated. In addition, the study will gather feedback from participants and parents to understand how this regimen impacts treatment satisfaction and quality of life compared to traditional therapy.
Managing T1D is not just about numbers, it’s about giving patients the freedom to live life. Reducing the complexity and discomfort of treatment may help families feel more confident and less stressed, especially during the early “honeymoon” phase when insulin needs can change rapidly. If inhaled insulin proves to be a meaningful alternative for newly diagnosed pediatric patients with type 1 diabetes, it could provide children and families greater flexibility while potentially improving adherence and outcomes.
Ultimately, the INHALE‑1st study aims to provide evidence that supports continued innovation in diabetes care. By offering an innovative alternative to insulin delivery, Afrezza seeks to make life with T1D simpler, safer, and more sustainable, helping children live healthier, more active lives without the constant burden of multiple daily injections.
Anticipated Outcome
INHALE-1st is expected to generate clear evidence on whether inhaled Technosphere Insulin (TI; Afrezza) used with once-daily basal insulin (TI-BI) can be used safely in youth newly-diagnosed with type 1 diabetes (T1D) and whether it can support meaningful glucose management during the first months after diagnosis. Rather than assuming this benefit, the study is designed to measure, using objective glucose data, safety monitoring, patient reported experience, and related monitoring measures, whether this approach can be a viable alternative to traditional mealtime injections in this early stage of care. Importantly, the initial dosing experience will follow weight-based dosing principles consistent with ISPAD guidelines, providing clinicians with practical guidance on how to initiate Afrezza in this population and support optimal clinical care during the transition to inhaled insulin.
The main outcome the study will aim to address is how many participants achieve strong CGM time-in-range: spending at least 70% of time between 70-180 mg/dL during the two week before the end of the initial treatment phase. The study will also describe related CGM measures (including average glucose, time-in-tighter- range of 70-140 mg/dL, and time spent high or low) and track HbA1c at scheduled timepoints.
Safety outcomes will include monitoring for severe hypoglycemia, diabetic ketoacidosis (DKA), asthma diagnosis, and breathing-related issues, with periodic lung function testing using spirometry (including percent predicted FEV1). To capture real-world usability, the study will measure satisfaction and perceived burden through surveys and interviews, as well as track how many participants continue TI-BI beyond the initial 13-week phase (including the optional 26 week extension). If study results support an acceptable benefit-risk profile in this population, INHALE-1st could help clinicians and families have additional options when it comes to mealtime insulin treatment and help move more patients towards improved treatment outcomes.
Relevance to T1D
INHALE-1st is designed to evaluate time-in-range (TIR), the percentage of time glucose stays between 70 and 180 mg/dL as measured by continuous glucose monitoring (CGM). The American Diabetes Association recognizes TIR and related CGM metrics as important indicators of day-to-day diabetes management that complement HbA1c. In INHALE-1st, the primary outcome is the percentage of participants who achieve at least 70% TIR during the two weeks before the 13-week visit, providing a clear, clinically interpretable measure of how well glucose levels are managed in real life.
This focus is highly relevant to children and teens with type 1 diabetes because daily management is heavily shaped by meals, activity, school schedules, and rapid changes in insulin needs, especially soon after diagnosis. If INHALE-1st demonstrates that inhaled mealtime insulin combined with basal insulin can be used safely while supporting target TIR, it could broaden early treatment options with a needle-sparing approach that is responsive to CGM feedback and practical for everyday routines.
By pairing a fast-acting mealtime insulin strategy with CGM-based outcomes and patient experience measures, the study aims to generate evidence that matters to families and clinicians: not just whether glucose targets can be met, but whether care can be delivered in a way that fits the realities of pediatric life.