Michael Monostra , 2025-06-22 19:07:00
Key takeaways:
- Technsophere insulin conferred a similar HbA1c as a rapid-acting analog for children and adolescents with diabetes.
- Those receiving technosphere insulin gained less weight and were more satisfied with therapy.
CHICAGO — Inhaled insulin is an “important alternative” to injected rapid-acting analog insulin for children and teens with diabetes, according to a speaker at the American Diabetes Association Scientific Sessions.
Healio previously reported data from the INHALE-3 trial that demonstrated technosphere insulin (Afrezza, MannKind Pharma), a rapid-acting human insulin administered via an inhaler, was noninferior to usual care for adults with type 1 and type 2 diabetes. New data from the INHALE-1 trial presented at the American Diabetes Association Scientific Sessions shows similar findings in children and adolescents with diabetes: those assigned technosphere insulin had a similar HbA1c level at 26 weeks compared with participants assigned rapid-acting analog insulin.
“The take-home message is that inhaled insulin is safe and effective in children with diabetes,” Michael Haller, MD, professor and chief of pediatric endocrinology at University of Florida, told Healio. “Inhaled insulin performed as well as injected rapid acting insulin on average and, for some patients, inhaled insulin proved to provide superior glycemic control with improved satisfaction scores and reduced weight gain.”
HbA1c similar between groups
The INHALE-1 trial enrolled 230 children and adolescents aged 4 to 17 years with type 1 or type 2 diabetes who were receiving multiple daily insulin injections at baseline (mean age, 12.6 years; 38% female; 98% type 1 diabetes). Participants were randomly assigned to receive technosphere insulin or rapid-acting analog insulin for 26 weeks. All participants used basal insulin and a real-time continuous glucose monitor (Dexcom G6).
The primary outcome was HbA1c at 26 weeks. The technosphere insulin group had an increase in HbA1c from 8.22% at baseline to 8.41% at 26 weeks. HbA1c was 8.21% in the rapid-acting analog group at baseline and at 26 weeks. In a sensitivity analysis that excluded a single extreme nonadherent outlier, the difference in the primary outcome was 0.14% (P = .026 for noninferiority), according to the presentation.
In the technosphere insulin group, 10% had an HbA1c less than 7% at 26 weeks. HbA1c improved by 0.5 percentage points for 15% of youths assigned technosphere insulin and worsened by 0.5 percentage points or more for 29% of those in that group.
Haller said technosphere insulin is more rapid-acting than injectable insulins and using the product requires some adjustments by the patient.
“The patients who do really well have to know they are going to use technosphere insulin multiple times a day and even multiple times following a single meal,” Haller said. “It requires tune-ups fairly frequently, because while it is the most rapid insulin available, it also clears from the body quickly. We realize this approach is not for everyone. In the spirit of giving people with a lifelong diagnosis a broad range of tools to manage their diabetes, inhaled insulin is an important addition to the toolbox.”
Haller also said adjustments to the dosing oftechnosphere insulin may be needed. As injected and inhaled units are not equivalent, in the INHALE-1 trial, the starting dose of technosphere insulin was double the units of the participant’s rapid-acting analog dose, rounded down to the nearest 4U cartridge, with 4U, 8U and 12U cartridges available. At 26 weeks, those using technosphere insulin were receiving a dose 2.96-times greater than the rapid-acting analog dose at baseline.
Secondary outcomes
The researchers reported no significant difference in time in range with a glucose of 70 mg/dL to 180 mg/dL between the technosphere insulin and rapid-acting analog groups at 26 weeks (39% vs. 41%; P = .38). Those assigned technosphere insulin had a lower BMI percentile (treatment difference, –4.2 percentile; 95% CI, –7.4 to –0.9; P = .009) at 26 weeks.
Among participants aged 13 years and older, those assigned technosphere insulin had higher diabetes treatment satisfaction than their peers assigned rapid-acting analog insulin. Similarly, parents of children aged younger than 13 years reported higher treatment satisfaction with technosphere insulin (P = .004).
“It’s not always about glycemic outcomes, though inhaled insulin performs well in that regard; it’s also about giving people a sense of ownership over their disease and choice in how to manage it,” Haller said.
Safety data
A higher proportion of participants assigned technosphere insulin reported at least one adverse event compared with rapid-acting analog insulin (75% vs. 66%). Severe hypoglycemia occurred in two youths in the technosphere insulin group and one in the rapid-acting analog group. There were no reports of diabetic ketoacidosis among those receiving technosphere insulin and one event in the rapid-acting analog group. There was no difference in hypoglycemia rates between the two groups.
In the technosphere insulin group, 17% reported cough during inhalation. Haller said the cough was typically mild and is consistent with what has been observed in the adult trials. There was no significant difference in percent of predicted forced expiratory volume in 1 second between the two groups, which indicates that technosphere insulin did not impact pulmonary function among children, Haller added.
“People shouldn’t have concerns with the safety of the drug,” Haller said. “Afrezza was remarkably safe to use in children with diabetes.”
A new indication?
Technosphere insulin is not currently FDA-approved for use in children and adolescents. However, Haller said the data from INHALE-1 should be strong enough for the FDA to consider an expanded indication.
“I think there are going to be opportunities to offer this to newly-diagnosed kids who are experiencing the life-changing event of a diabetes diagnosis,” Haller said. “Being able to say you can have one injection a day and manage the rest of your diabetes with an inhaled product is very attractive as you’re transitioning to this new lifelong diagnosis.”
Haller said technosphere insulin could eventually be used with automated insulin delivery systems and can also be beneficial for people who don’t want to use diabetes technology.
“I think these data open up a number of possibilities for the use of inhaled insulin in youths with type 1 diabetes,” Haller said.
For more information:
Michael Haller, MD, can be reached at hallemj@peds.ufl.edu.
Sources/Disclosures
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Haller M. From discovery to treatment – Latest updates on inhaled insulin treatment. Presented at: American Diabetes Association Scientific Sessions; June 20-23, 2025; Chicago.
Disclosures:
Haller reports serving on advisory board(s) for MannKind and consulting and receiving research grants from MannKind and Sanofi.
