Findings from INHALE-3, a trial examining the use of inhaled insulin in adults with type 1 diabetes, demonstrated the safety and efficacy of inhaled insulin in improving glycemic control, suggesting a potential role for inhaled insulin as an alternative insulin solution to enhance diabetes management. The findings were presented by a panel of the study investigators during a Saturday, June 22, symposium.

“This was a positive outcome because we learned so much about how to use this novel insulin,” said INHALE-3 Study Chair Irl B. Hirsch, MD, University of Washington (UW) School of Medicine and UW Medicine Diabetes Institute, who discussed the implications of the key findings of the study. “We learned that using inhaled insulin may be good for patients who are engaged in their diabetes self-management and want to reduce hyperglycemia even further, and it may be good for patients who want an alternative to a pump.”

In INHALE-3—a Phase 4, randomized controlled trial—approximately 120 participants with type 1 diabetes using multiple daily injections, an automated insulin delivery (AID) system or a pump without automation, and continuous glucose monitoring (CGM) were randomly assigned to an insulin regimen of insulin degludec plus inhaled insulin Afrezza and CGM or continuation of usual care.

Overall, the study authors reported that more participants using the inhaled insulin regimen experienced significant improvements in A1C levels compared to those on usual care, noting that 21 percent of those on inhaled insulin had an A1C improvement of greater than 0.5 percent, while this was seen in only 5 percent of those with standard care.

“Importantly, for those who started with an A1C above 7 percent, absolutely nobody in the usual care group got below 7 percent at the end, whereas it was 21 percent in those with the inhaled insulin,” Dr. Hirsch said.

The primary outcome of the trial was at 17 weeks, followed by a 13-week extension phase in which participants in both groups used the degludec-inhaled insulin regimen.

The study’s primary endpoint was a change in A1C levels. Secondary endpoints included changes in time-in-range (TIR) and hypoglycemia measured via CGM and patient-reported outcomes on insulin delivery satisfaction.

The study also found that 19 percent of participants who switched from using an AID system to using inhaled insulin plus degludec achieved an A1C improvement greater than 0.5 percent. In contrast, 26 percent of the patients in the inhaled insulin group had a worsening of A1C greater than 0.5 percent compared to 3 percent with standard care, demonstrating that “one size does not fit all” in the use of inhaled insulin, Dr. Hirsch noted.

“The bottom line is we need to understand appropriate dosing for both the inhaled and the basal insulin,” Dr. Hirsch said. “It’s really important to have that right dose of basal insulin, and it is important for the clinical care team to understand how patients can get their best results from this therapy.”

Thomas Blevins, MD, Texas Diabetes and Endocrinology, concluded the symposium with comments on the significance of the study and how the findings might impact the use of inhaled insulin in clinical practice.

“We learned a lot from INHALE-3,” Dr. Blevins said. “There are a number of reasons to use inhaled insulin: It controls the postprandial spike very effectively; rapid in/rapid out is important, so there is less chance of stacking; and it is discreet and convenient.”

There are also important reasons not to use inhaled insulin, he noted, including for patients with chronic or recurrent pulmonary disease, such as asthma or chronic obstructive pulmonary disease (COPD), or patients who have hypersensitivity to regular insulin (human).

“Pulmonary function tests need to be done. This is a practical step we can do in our offices,” Dr. Blevins said. “We should assess pulmonary function with spirometry at baseline and every six months of therapy, even when there are no pulmonary symptoms.”

Moving forward, Dr. Blevins said it will be important to further define guidelines and best practices for the use of inhaled insulin. However, it will ultimately be up to patients and their providers to determine whether the therapy is right for them.

Other speakers during the symposium included:

• Halis K. Akturk, MD, Barbara Davis Center for Diabetes, who discussed the history of inhaled insulin and the study rationale.
• Yogish C. Kudva, MD, Mayo Clinic, who described the study methods and the baseline characteristics of participants.
• Ruth S. Weinstock, MD, PhD, SUNY Upstate Medical University, who reviewed results related to the study’s in-clinic meal challenges
• Carol J. Levy, MD, CDCES, Icahn School of Medicine at Mount Sinai, who reported the primary efficacy, safety, and quality-of-life outcomes of the study.
• Grazia Aleppo, MD, FACE, FACP, Northwestern University, Feinberg School of Medicine, who reviewed key subgroup findings from the study.

The symposium, The Efficacy and Safety of Inhaled Insulin Used with Insulin Degludec Compared with Automated Insulin Delivery or Multiple Daily Insulin Injections in Adults with Type 1 Diabetes—Results of the INHALE-3 Randomized Trial, can be viewed on-demand by registered meeting participants on the virtual meeting platform. If you haven’t registered for the 84^th Scientific Sessions, register today to access the valuable meeting content through Aug. 26.