INHALE-3 underpins alternate insulin delivery method for T1D

Findings from the phase IV INHALE-3 trial support inhaled insulin for the management of type 1 diabetes (T1D) in adults, underlining its role as an alternative insulin solution to enhance diabetes management.

“We learned that using inhaled insulin may be good for patients who are engaged in their diabetes self-management and want to reduce hyperglycaemia even further, and it may be good for patients who want an alternative to a pump,” said study chair Dr Irl Hirsch from the University of Washington, Seattle, Washington, US, during a symposium at ADA 2024.

The fraction of participants achieving HbA_1c <7 percent at 17 weeks was nearly twofold higher in the inhaled-insulin group as opposed to those who were on usual care (UC; 30 percent vs 17 percent). [Hirsch, et al, ADA 2024]

“Importantly, for those who had a baseline HbA_1c >7 percent, absolutely nobody in the UC group got to <7 percent HbA_1c level at 17 weeks, whereas among those in the inhaled-insulin group, 21 percent [achieved this outcome],” noted Hirsch.

Moreover, more participants on the inhaled insulin regimen had HbA_1c reduction of >0.5 percent vs those on UC, both in the overall cohort (21 percent vs 5 percent) and in the HbA_1c >7 percent subgroup (28 percent vs 7 percent).

Safety-wise, only one patient in the inhaled-insulin group had a severe hypoglycaemia event. The most pronounced adverse event tied to inhaled-insulin use was cough.

“However, cough was typically mild, occurred at the time of inhalation, and in most cases, it did not [interfere with the use of] inhaled insulin,” said Dr Carol Levy from the Icahn School of Medicine at Mount Sinai, New York City, New York, US, who presented the efficacy and safety outcomes at ADA 2024. She added that the cough events were transient and easily resolved with water intake.

Not for everyone

However, over a quarter (26 percent) of participants on inhaled insulin had worsening of HbA_1c >0.5 percent; with UC, the corresponding rate was 3 percent. A similar trend was seen among those with baseline HbA_1c >7 percent (21 percent vs 2 percent).

According to Hirsch, these findings imply that the use of inhaled insulin is not for every T1D patient and thus, not a ‘one-size-fits-all’ solution.

“The bottomline is we need to understand appropriate dosing for both inhaled and basal insulin,” Hirsch stressed. “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.”

To inform clinical decisions, tailor treatment plans

INHALE-3 included 123 T1D patients (mean age 45 years, 54 percent women, mean HbA_1c 7.6 percent) who were using traditional insulin delivery methods such as multiple daily injections, an automated insulin delivery system or a pump without automation, and continuous glucose monitoring (CGM).

Participants were randomized 1:1 to either insulin degludec plus inhaled insulin and CGM, or to continue UC and CGM, for 17 weeks (dose was titrated during the first 4 weeks). A 13-week extension phase ensued thereafter, wherein all participants were placed on the insulin degludec-inhaled insulin regimen.

“[The] findings will impact diabetes management by providing healthcare providers and patients with an alternative insulin delivery method,” Hirsch said. “The results will assist in better informing clinical decisions and tailoring treatment plans to individual patient needs, potentially improving adherence, patient satisfaction, and overall outcomes.”

Further studies are warranted to ascertain the impact of inhaled insulin in a broader patient population, including paediatric and pregnant cohorts, to fortify its role in comprehensive diabetes management.

The pivotal AFFINITY trials have led to the 2014 FDA approval of inhaled insulin for diabetes management. [Diabetes Care 2015;38:2266-2273; Diabetes Care 2015;18:2274-2281; https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022472lbl.pdf, accessed July 1, 2024]