The rapid-acting inhaled insulin Afrezza (technosphere insulin) demonstrated sustained efficacy and increasing dosage requirements over 30 weeks in adults with type 1 diabetes, according to extended data from the INHALE-3 clinical trial presented at recent endocrinology conferences.
Dosing Patterns Show Adaptation Over Time
Among 35 adults who completed both the main INHALE-3 trial and its extension phase, 74% increased their daily technosphere insulin dose by more than 4 units over the 30-week period, according to Jennifer Rittenberry, MD, medical science liaison at MannKind Corp.
The total daily inhaled insulin dose progressively increased from 36 units at 4 days to 48 units at 17 weeks, ultimately reaching 52 units by week 30. Notably, the proportion of total insulin that consisted of bolus insulin rose from 60% at 4 days to 70% by study completion.
"Every patient has individual insulin needs that can change based on meal patterns, physical activity, illnesses or medications," Rittenberry explained during her presentation at the American Association of Clinical Endocrinology Annual Scientific and Clinical Conference. "This study helps characterize what typical technosphere insulin doses are."
While 8-unit doses remained the most common per-meal dosage throughout the study, the data revealed a clear trend toward higher doses over time. By week 30, doses of 12 and 16 units became increasingly common, with fewer patients using the lowest available 4-unit cartridge.
Significant HbA1c Improvements
The INHALE-3 extension study demonstrated meaningful glycemic benefits for participants. Patients who used technosphere insulin throughout the entire 30-week period saw their HbA1c decline from 7.6% at 17 weeks to 7.4% at 30 weeks (P < .001).
Even more striking was the increase in patients achieving target glycemic control. The proportion of adults with an HbA1c below 7% rose from 21% at baseline to 30% at 17 weeks and reached 42% by week 30.
Irl Hirsch, MD, professor of medicine at the University of Washington School of Medicine and an INHALE-3 investigator, noted the therapy's particular benefit for patients with higher baseline HbA1c levels. Among those starting above 7%, 21% of the technosphere insulin group achieved an HbA1c below 7% by week 17, compared to none in the usual care group.
"This therapy isn't for everybody, but for many patients, this therapy was spectacular," Hirsch stated during a symposium at the International Conference on Advanced Technologies & Treatments for Diabetes.
Crossover Results Confirm Efficacy
The extension study also allowed patients from the original control group to switch to technosphere insulin, providing additional evidence of the therapy's effectiveness.
These crossover patients experienced a mean HbA1c decline from 7.59% to 7.36% after just 13 weeks of treatment (P < .001 for noninferiority; P = .02 for superiority). The percentage of adults achieving an HbA1c below 7% more than doubled, rising from 14% to 31%.
Administration Timing Critical for Success
Researchers emphasized that proper administration is essential for maximizing the benefits of inhaled insulin. Unlike traditional rapid-acting analogs that require waiting 10-30 minutes before eating, technosphere insulin should be taken at the start of a meal.
"You don't want to wait 10, 15, 20, 30 minutes like we do with rapid-acting analogs," Hirsch advised. "You need to give [technosphere] insulin at the start of the meal."
Meal challenge data from INHALE-3 confirmed that when properly timed, technosphere insulin resulted in lower postprandial glucose increases compared to rapid-acting analog insulin.
Safety Profile Remains Consistent
Throughout both the main trial and extension phase, no new safety signals emerged. One severe hypoglycemic event was reported during the extension study in a participant who had switched from usual care. According to Rittenberry, this occurred due to a delay in starting a meal after administering technosphere insulin, highlighting the importance of proper timing.
The most commonly reported adverse event was cough, consistent with previous studies of inhaled insulin formulations.
Clinical Implications
The INHALE-3 data suggests technosphere insulin could be a valuable alternative for certain patients with type 1 diabetes, particularly those seeking alternatives to insulin pumps or those struggling to achieve target glycemic control with traditional insulin regimens.
However, Hirsch emphasized that successful use requires patient engagement and proper education on administration techniques. Clinical care teams need to work closely with patients to determine optimal dosing strategies and ensure they understand the unique pharmacokinetic profile of inhaled insulin.
As the study demonstrates, dosing requirements typically increase over time, necessitating ongoing assessment and adjustment to maintain glycemic benefits.
