INHALE-3 Study Data Shows Diabetes Care Is Not “One-Size-Fits-All”

Author(s):

Ashley Gallagher, Associate Editor

Many patients who took technosphere insulin saw improvements in hemoglobin A1c, but other patients saw worsening with the drug.

Approximately 30% of individuals with type 1 diabetes (T1D) who took technosphere insulin (Afrezza, insulin human inhalation powder; Mannkind) plus basal insulin reached a hemoglobin A_1c (HbA_1c) of less than 7% at 17 weeks compared with 17% in the usual care group, which included multiple daily injections (MDIs), automated insulin delivery (AID) systems, or a pump without automation. The results to the INHALE-3 (NCT05904743) study were presented at the American Diabetes Association 84th Scientific Sessions in Orlando, Florida.^1,2

Image Credit: Vitalii Vodolazskyi - stock.adobe.com

“Somebody who is coming in with an [Hb]A_1c above 7%, what we showed was that the inhaled insulin did better than the MDI in general, but not as well as the AID, but I still think the more important point of the whole thing is that depending on the patient, and their personality, and their phenotype, and their engagement, we had all of these AID people who actually did better,” Irl Hirsch, MD, professor of Medicine and Diabetes Treatment and Teaching Chair at the University of Washington, said in an interview with Pharmacy Times^®.

The randomized control trial included treatment randomization for patients with degludec plus technosphere insulin and Dexcom G7 or the usual care of AID, MDI, or pump without automation and a personal continuous glucose monitoring (CGM). The study was 17 weeks long, with the first 4 weeks serving as the dose titration. Furthermore, both groups used technosphere insulin in a 13-week extension phase, according to Yogish Kudva, MD, professor of endocrinology, diabetes, metabolism, and nutrition, at Mayo Clinic, in the presentation. For technosphere insulin, the starting dose was equal to the total daily basal units through the pump or injection, with titrating every 3 to 5 days through the first 10 days and then weekly through week 4 and through the trial. Furthermore, meal dose titrated was included based on 1-hour post-prandial CGM, according to Kuduva. A correction dose could be given after initial dose.²

For the usual care group, individuals continued their pre-study insulin delivery and usual diabetes management.²

Nineteen sites in the United States participated in the study, including individuals aged older than 18 years, having T1D for at least 6 months, having an HbA_1c of less than 11%, having the same insulin delivery method for 3 months, and using a CGM on a regular basis. There were 123 individuals included with a mean age of 45 years and 54% being female. The mean diabetes duration was 23 years, 89% were white, ad 89% were non-Hispanic. Approximately 42% had education less than a bachelor’s degree, 41% had less than $100,000 income, 81% had private insurance, and the mean body mass index was 27.9 kg/m².²

Investigators found that 21% of those in the technosphere insulin group compared with 0% of those in the usual care group met the HbA_1c goals of less than 7%, if baseline was greater than 7%. Furthermore, there were no differences in CGM measured hyperglycemia in the groups and the titrated basal-bolus ratio was approximately 70/30 for technosphere insulin and 50/50 for the usual care. Approximately half of individuals expressed an interest in continuing technosphere insulin.¹

Carol Levy, Md, CDCES, endocrinologist at Mount Sinai, said that the primary outcome was non-inferiority, which was met in the study. However, the investigators noted that some patients who switched from usual care to technosphere insulin had worsening, which they said could be due to missing doses of inhaled insulin or underdosing before bed. Levy said that approximately 26% had worsened HbA_1c greater than 0.5% with technosphere insulin compared with 3% on the usual care. Approximately 21% had improved HbA_1c with technosphere insulin compared with 5% in the standard of care.^1,2

About The Study

Trial Name: INHALE-3: Afrezza Combined With Insulin Degludec Versus Usual Care in Adults With Type 1 Diabetes

ClinicalTrials.gov ID: NCT05904743

Sponsor: Mannkind Corporation

Completion Date (Estimated: October 2024

“The usual care group was using their usual care and stayed about the same. There wasn’t a broad change,” Levy said. “Some individuals did incredibly well on technosphere insulin while other struggled more.”²

For those with a baseline of greater than 7%, there was an improved HbA_1c of 28% with technosphere insulin compared with 7% for the standard of care, but a worsening for 21% compared with 2%, respectively. As for safety, 77% of those in the technosphere insulin group experienced adverse events (AEs), with only 1 severe hypoglycemia even, and 64% in the usual care group experienced AEs with 1 experiencing hospitalization for hyperglycemia/ketosis and 1 for appendectomy. The most common AE for the technosphere insulin group was cough, with 14 events, and the second most common was shortness of breath, with 5 events.²

The results to the 13-week expansion will be presented at a future medical conference.¹

References

Inhale-3 study reveals positive readout in head-to-head comparison of inhaled insulin vs. usual care in T1D; new data presented at the American Diabetes Association’s 84th Scientific Session. News release. Mannkind. June 22, 2024. Accessed July 2, 2024. Email.
Back Rw, Akturk HK, Weinstock RS, Aleppo G, Blevin T. 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. At: ADA 84th Scientific Sessions; June 21-June 24, 2024; Orlando, Florida.