Inhaled insulin lowers HbA1c at 30 weeks in adults with type 1 diabetes
Key takeaways:
- Technosphere insulin was tied to improvements in HbA1c for adults with type 1 diabetes.
- Proper dosing at mealtimes is essential for maximizing glycemic benefits with technosphere insulin.
Technosphere insulin, a rapid-acting human insulin administrated through an inhaler, was associated with reductions in HbA1c at 30 weeks for adults with type 1 diabetes, according to findings from the INHALE-3 extension trial.
As Healio previously reported, technosphere insulin (Afrezza, MannKind Pharma) resulted in noninferior HbA1c changes compared with usual care in adults with type 1 diabetes participating in the INHALE-3 randomized controlled trial. During a symposium at the International Conference on Advanced Technologies & Treatments for Diabetes, data from the INHALE-3 extension trial were presented showing adults in the technosphere insulin group had a reduction in HbA1c from the end of the 17-week primary trial to 30 weeks. Adults in the usual care group during INHALE-3 who switched to technosphere insulin during the extension trial were also able to reduce their HbA1c.
The findings revealed that technosphere insulin could be an important tool in glycemic management for some adults with type 1 diabetes, though patients must be vigilant about the timing of administration, according to Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology and nutrition at the University of Washington School of Medicine and an investigator on the INHALE-3 trial.
“Using technosphere insulin may be good for patients, [but] they have to be engaged in their diabetes self-management, [and] want to reduce their hyperglycemia even further,” Hirsch said during the presentation. “Using technosphere insulin may be good for patients who want an alternative to an [insulin] pump. Not everybody wants a pump, we have a lot of our patients who didn’t want to carry it, and they are still on technosphere insulin to this day.”
INHALE-3 takeaways
In the 17-week INHALE-3 trial, 123 adults with type 1 diabetes were randomly assigned to technosphere insulin plus insulin degludec (Tresiba, Novo Nordisk) with use of a Dexcom G7 continuous glucose monitor, or usual care with participants using their own CGM.
At 17 weeks, technosphere insulin was deemed noninferior to usual care, with the inhaled insulin group having an HbA1c of 7.6% vs. a 7.5% HbA1c for the usual care group (P = .01 for noninferiority).
Hirsch noted the technosphere insulin group had variation in their response to the agent. While 21% of the technosphere insulin group reduced their HbA1c by 0.5 percentage points or more, 26% had an HbA1c increase of 0.5 percentage points or more at 17 weeks. Of the usual care group, 5% had an HbA1c reduction of 0.5 percentage points or more and 3% had their HbA1c increased by 0.5 percentage points or more.
Hirsch said technosphere insulin had a positive impact on adults with a higher baseline HbA1c. Among adults with a baseline HbA1c of 7% or higher, 21% of adults in the technosphere insulin group had an HbA1c of less than 7% at 17 weeks vs. none in the usual care group. The proportion of adults with a baseline HbA1c above 7% who reduced their HbA1c by 0.5 percentage points or more was 28% with technosphere insulin and 7% with usual care. The percentage of participants with an HbA1c increase of 0.5 percentage points or more was 21% with technosphere insulin and 2% with usual care among those with a higher baseline HbA1c.
“This therapy isn’t for everybody, but for many patients, this therapy was spectacular,” Hirsch said.
Benefits in extension study
Participants in INHALE-3 were invited to continue to a 13-week extension study. Adults originally assigned to technosphere insulin could continue to use the therapy, and those randomly assigned to usual care were permitted to start technosphere insulin.
Of adults who used technosphere insulin in INHALE-3 and continued onto the extension study, HbA1c declined from 7.6% at 17 weeks to 7.4% at 30 weeks (P < .001). The proportion of adults with an HbA1c of less than 7% rose from 21% at INHALE-3 baseline to 30% at 17 weeks and 42% at 30 weeks.
Adults who switched from usual care to technosphere insulin had a mean HbA1c decline from 7.59% at the start of the extension study to 7.36% at 13 weeks (P < .001 for noninferiority; P = .02 for superiority). The proportion of adults with an HbA1c of less than 7% rose from 14% at baseline to 31% at 13 weeks. Of the group, 29% had an HbA1c decrease of 0.5 or more percentage points from baseline to 13 weeks, and 12% had an HbA1c increase of 0.5 or more percentage points.
Tips for using technosphere insulin
Hirsch also presented meal challenge data from INHALE-3, which revealed technosphere insulin resulted in a lower postprandial glucose increase compared with rapid-acting analog insulin. However, Hirsch noted people with type 1 diabetes need to be taking the optimal dose of technosphere insulin to receive the full benefit.
“What we use with rapid-acting analog [insulin], there isn’t a simple conversion for everybody,” Hirsch said. “There’s a bit of trial and error.”
Hirsch shared several tips for adults to have successful glycemic management with technosphere insulin. He said patients should optimize their basal insulin dose and be willing to repeat using technosphere insulin 1 to 3 hours after a meal as well as before going to sleep to avoid hyperglycemia overnight. Hirsch added the timing of dosing is also important.
“You don’t want to wait 10, 15, 20, 30 minutes like we do with rapid-acting analogs,” Hirsch said. “You need give [technosphere] insulin at the start of the meal.”
Hirsch added clinical care teams need to work with patients to determine how they can receive the maximum benefits from technosphere insulin.
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Hirsch IB. Parallel Session 14: From past to present: Investigating the spectrum of insulins. Presented at: International Conference on Advanced Technologies & Treatments for Diabetes; March 19-22, 2025; Amsterdam (hybrid meeting).
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