New data from the INHALE-3 trial presented at the 84th American Diabetes Association Scientific Sessions demonstrate that inhaled insulin represents a viable alternative for improving glycemic control in adults with type 1 diabetes. The phase 4 randomized trial compared inhaled insulin (Afrezza) plus degludec insulin against usual care, providing evidence for an alternative insulin delivery method that could enhance diabetes management.
Trial Design and Patient Population
INHALE-3 enrolled 123 adult patients with type 1 diabetes from 19 centers across the United States. The trial featured a 17-week randomized period followed by a 13-week extension period. Participants were divided into two groups: one receiving inhaled insulin plus degludec insulin, and the other continuing their usual care regimen, which included automated insulin delivery systems in approximately 50% of patients or multiple daily injections.
The study's primary endpoint focused on changes in HbA1c levels, a critical marker of long-term blood glucose control. Secondary endpoints included changes in time-in-range, hypoglycemia measured with continuous glucose monitoring, and patient-reported outcomes on insulin delivery satisfaction.
Significant HbA1c Improvements Observed
The trial results revealed notable improvements in glycemic control among participants using the inhaled insulin regimen. Analysis showed that 21% of those on inhaled insulin experienced an HbA1c improvement of greater than 0.5%, compared to only 5% of those receiving standard care.
Among participants who had an HbA1c level of 7% or greater at baseline, 21% of the inhaled insulin cohort achieved the target HbA1c goal of less than 7%. In stark contrast, no patients in the usual care group meeting these criteria achieved this glycemic target.
Particularly noteworthy was the finding that 19% of participants who switched from using an automated insulin delivery system to the inhaled insulin plus degludec regimen achieved an HbA1c improvement greater than 0.5%.
Mixed Clinical Outcomes Highlight Patient Variability
While the trial demonstrated promising results for many participants, the data also revealed that the inhaled insulin regimen was not universally beneficial. The study found that 26% of patients in the inhaled insulin group experienced a worsening of HbA1c greater than 0.5%, compared with only 3% in the standard care group.
Despite these mixed outcomes, over half of the study participants expressed a desire to continue using inhaled insulin after the trial's completion, suggesting potential benefits in patient satisfaction and treatment adherence.
Clinical Implications and Future Directions
"The INHALE-3 study's findings will impact diabetes management by providing healthcare providers and patients with an alternative insulin delivery method," said principal investigator Irl B. Hirsch, MD, from the University of Washington. "These results will assist in better informing clinical decisions and tailoring treatment plans to individual patient needs, potentially improving adherence, patient satisfaction, and overall outcomes."
The approval of inhaled insulin by the FDA in 2014 came with specific guidelines for use in combination with long-acting insulin in patients with type 1 diabetes. The agency also issued a Boxed Warning related to risks among patients with decreased pulmonary function and required the creation of a Risk Evaluation and Mitigation Strategy (REMS) program.
Building on the INHALE-3 results, future research will focus on broader patient populations, including pediatric patients and pregnant women, to further establish the role of inhaled insulin in comprehensive diabetes care. Type 1 diabetes affects 11.6% of the American population and millions of individuals globally, requiring ongoing insulin therapy to manage blood glucose levels.
