Roy Beck, MD, PhD, is the founder of the Jaeb Center for Health Research.

Roy Beck, MD, PhD

INHALE-1: Afrezza Safe but Misses HbA1c Endpoint in Children With T1D or T2D, 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.

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. 

 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 

. “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 

. 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.

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.

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.

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 

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 (

 = .004) and had less gain in weight and BMI percentile (

“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.

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. 

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

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Beck discusses the recently presented results of INHALE-1, in which technosphere insulin failed to prove noninferiority to RAA but had no pulmonary effects.

INHALE-3 Analysis Supports Need for Increased Technosphere Insulin Doses, With Roy Beck, MD, PhD

Technosphere insulin (TI), an ultrarapid-acting inhaled insulin, has shown its efficacy in glucose management in higher doses than have been approved for adults with 

, according to an analysis from INHALE-3.

“One of the challenges that we have in treating patients with injectable insulin is that it’s injected underneath the skin,” Roy Beck, MD, PhD, founder of the Jaeb Center for Health Research, told 

 in an exclusive interview. “It takes some time to be absorbed into the bloodstream, and so there’s a delay much greater than what we see with a pancreas producing insulin normally. When insulin is inhaled and goes into the lung, it distributes into the bloodstream very rapidly and becomes something very close to endogenous insulin.”

TI is the first and only ultrarapid-acting inhaled insulin to receive approval from the 

 for the improvement of glycemic control in patients with diabetes mellitus. Initially approved under the brand name Afrezza, TI received an update to its prescribing information on January 26, 2026, revising the recommendations for starting mealtime dosage when patients switch from subcutaneous mealtime insulin regimens.

INHALE-3 was a multicenter, randomized, controlled study comparing the safety and efficacy of TI combined with insulin degludec versus standard care in adults with T1D. This latter group included treatment regimens of multiple daily injections or insulin pump therapy, including automated insulin delivery (AID) systems. Patients were not blinded to treatment.

Upon randomization, patients in the TI treatment arm transitioned from their previous insulin therapy using a conversion ratio modified from existing recommendations, wherein the TI dose is calculated by multiplying the patient’s usual subcutaneous rapid-acting insulin analogue (RAA) dose by 2 and rounding down to the nearest available cartridge size from among 4, 8, or 12 U, or a combination thereof. The first dose of TI was administered in-clinic, after which patients were instructed to titrate their TI dose over time based on glucose response.

The present analysis analyzed a specific subgroup of patients who had been randomized to the T1D and degludec arm and had complete insulin dosing data at all 3 key timepoints – baseline, week 17, and week 30. Patients were eligible for inclusion if they had non-missing data for total daily insulin doses and mealtime dosing at each time point. A total of 35 patients from INHALE-3 met these criteria and were included.

Among these patients, the mean age was 46 years with a baseline A1c of 7.72% (standard deviation [SD] +/- 1; 61 mmol/mol). Prior to TI initiation, 40% of participants were using AID. The mean baseline bolus and basal dose of RAA insulin were 23.9 U/d, with a bolus/basal ratio of roughly 50%/50%. After 30 weeks of monitoring, mean total daily TI dose increased from 36 U at baseline to 48 U at 17 weeks (

 <.001). By 30 weeks, the TI bolus/basal ratio had also shifted to around 70%/30% (

 <.001). At 17 weeks, 57% of participants had increased their TI dose by >4 U, which then increased to 74% at 30 weeks. Notably, investigators recorded no new safety signals with TI treatment.

Given these data, the FDA’s approval of higher starting doses for TI is no surprise. Investigators did, however, emphasize that higher overall dosing requirements are needed to support individualized titration and help patients reach their glycemic goals.

“All patients could potentially improve with this, because everyone who has diabetes has the potential for a spike after they eat,” Beck said. “There’s a real benefit to trying to reduce that by getting insulin into the bloodstream faster, although the effect of that insulin goes away pretty quickly. There were a substantial proportion of participants who improved quite a bit, but there were some who didn’t, and I think it’s largely because it took a certain regimented approach to frequent inhaling if your glucose was still high.”

Rittenberry J, Sylvan J, Mycue L-E, Griparic L, Kaiserman K. Inhaled insulin dosing in a randomized trial in adults with type 1 diabetes. 

MannKind Corporation. MannKind Announces FDA Approval of Updated Afrezza Label Providing Starting Dose Guidance when Switching from Multiple Daily Injections (MDI) or Insulin Pump Mealtime Therapy. January 26, 2026. Accessed April 17, 2026. 

https://investors.mannkindcorp.com/news-releases/news-release-details/mannkind-announces-fda-approval-updated-afrezzar-label-providing

Beck discusses a recent analysis of the phase 4 trial comparing TI and degludec against standard treatment, highlighting the need for individualized titration.

Roy Beck, MD, PhD

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