Inhaled Insulin Could Improve Glycemic Control, HbA1c Compared to Usual Care in Type 1 Diabetes

Irl Hirsch, MD
Credit: UW Medicine

New data presented at the 84th American Diabetes Association Scientific Sessions suggest use of an inhaled insulin regimen (Afrezza) represents a safe and efficacious way of improving glycemic control and reaching HbA1c goals for adults with type 1 diabetes.

Known as INHALE-3, the trial, which compared use of inhaled insulin plus insulin degludec relative to usual care, adds further insight into the potential role of inhaled insulin as a more regular option for patients with type 1 diabetes.¹

“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, University of Washington, and lead author of the study.² “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 road to approval for inhaled insulin was a winding road fraught with setbacks. Approved by the US Food and Drug Administration in 2014, the first New Drug Application for the agent was filed in 2009. Following a Complete Response Letter, a resubmission, and an advisory committee, the agent received approval in June 2014.^3,4

The approval was based on efficacy of mealtime inhaled insulin from a trial where the agent was compared to mealtime insulin aspart among adult patients with type 1 diabetes, both in combination with basal insulin for 24 weeks. The approval of inhaled insulin outlines it should be used in combination with long-acting insulin in patients with type 1 diabetes. With the 2014 approval, the FDA issued a Boxed Warning with the agent related to risks among patients with decreased pulmonary function and also required the creation of a Risk Evaluation and Mitigation Strategy (REMS) program.^3,4

A phase 4 trial, INHALE-3 was designed with a 17-week randomized period and a 13-week extension period to assess the efficacy and safety of inhaled insulin plus degludec insulin against standard of care in patients with type 1 diabetes. Enrolling patients from 19 centers in the US, the trial randomized 123 adult patients to inhaled insulin plus degludec insulin or usual care. Investigators pointed out automated insulin delivery systems in approximately 50% of those in the usual care group.^1,2

The trial’s primary outcome of interest was the change in HbA1c levels. Secondary outcomes of interest for the trial included changes in time-in-range, hypoglycemia, and patient-reported outcomes on insulin delivery satisfaction.^1,2

Initial analysis demonstrated use of inhaled insulin was associated with significant improvement in HbA1c levels relative to usual care. When assessing changes in HbA1c, an improvement of 0.5% or greater was observed among 21% of those on inhaled insulin and 5% of those with usual care. Among participants who had an HbA1c level of 7% or greater at baseline, 21% of the inhaled insulin cohort achieved the HbA1c goal of less than 7%. In contrast, 0 patients in the usual care group meeting these criteria achieved an HbA1c goal of less than 7%.^1,2

Additionally, investigators highlighted 19% of participants who switched from using an automated insulin delivery system to using inhaled insulin plus degludec achieved an HbA1c improvement greater than 0.5%. However, investigators pointed out 26% of the patients in the inhaled insulin group had a worsening of HbA1c greater than 0.5% compared with 3% with standard care.^1,2

According to a release from the ADA, future research with inhaled insulin will focus on broader populations, such as pediatrics and pregnancy.²

References:

1. ^{Hirsh I. 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. Presented at: American Diabetes Association (ADA) 84th Scientific Sessions. June 21 - 24, 2024. Orlando, FL.}
2. ^{American Diabetes Association. Study Shows Promising Results for Inhaled Insulin as Treatment for Type 1 Diabetes. American Diabetes Association. June 22, 2024. Accessed June 22, 2024.}
3. ^{MannKind Corporation. Mannkind Corporation announces FDA approval of AFREZZA(R); a novel, rapid-acting inhaled insulin for the treatment of diabetes. MannKind Corporation. June 27, 2014. Accessed June 22, 2024. https://investors.mannkindcorp.com/news-releases/news-release-details/mannkind-corporation-announces-fda-approval-afrezzar-novel-rapid.}
4. ^{Drugs.com. Afrezza (insulin human [rdna origin]) FDA approval history. Drugs.com. Accessed June 22, 2024. https://www.drugs.com/history/afrezza.html.}