Inhaled insulin noninferior to usual care for adults with type 1 diabetes
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Key takeaways:
- Adults with type 1 diabetes receiving technosphere insulin had a similar HbA1c at 17 weeks as those receiving usual care.
- Individual outcomes with technosphere insulin varied more than among usual care.
ORLANDO — An inhaled insulin was noninferior to usual care for change in HbA1c and continuous glucose monitoring metrics among adults with type 1 diabetes, according to data from the INHALE-3 trial.
Technosphere insulin (Afrezza, MannKind Pharma) is a rapid-acting regular human insulin that is administered through an inhaler. The insulin was approved by the FDA in June 2014 for adults with type 1 and type 2 diabetes. New findings presented at the American Diabetes Association Scientific Sessions revealed the insulin provided similar glycemic benefits as usual care for adults with type 1 diabetes. HbA1c was similar to usual care for the technosphere insulin group, but there was variability among individual outcomes, with 21% of adults receiving inhaled insulin having a 0.5 percentage point improvement in HbA1c by the end of the trial and 26% of the technosphere insulin group having a worsening of HbA1c by 0.5 percentage points or more.
The outcomes point to the importance of patient education when initiating technosphere insulin and individualizing care for each person, according to Irl B. Hirsch, MD, professor of medicine at the University of Washington School of Medicine in Seattle.
“Technosphere insulin is not for everyone, but for some, it really is an important option,” Hirsch said during a presentation.
INHALE-3 was a randomized controlled trial enrolling 123 adults aged 18 years and older with type 1 diabetes for at least 6 months and an HbA1c of less than 11% (mean age, 45 years; 54% women; 89% white). Participants had to use CGM regularly, use the same insulin delivery for at least 3 months before the trial and receiving 20 U to 100 U total daily insulin to participate. Adults were randomly assigned, 1:1, to technosphere insulin plus insulin degludec (Tresiba, Novo Nordisk) and a Dexcom G7 CGM, or usual care with their own personal CGM for 17 weeks. Baseline data were gathered for 14 days using a Dexcom G6 Pro CGM. Blood draws were conducted to measure HbA1c and forced expiratory volume, which is a measure of the volume of air a person can exhale in 1 second. Patient-reported outcomes were also collected at baseline. Dose titration took place during the first 4 weeks of the study. CGM measures, HbA1c, forced expiratory volume and patient-reported outcomes were collected again at 17 weeks. The trial was tested for noninferiority, with the primary outcome being HbA1c at 17 weeks.
Technosphere insulin noninferior to usual care
At 17 weeks, technosphere insulin was noninferior to usual care, with the technosphere insulin group having an HbA1c of 7.6% and the usual care group having a 7.5% HbA1c (P = .01 for noninferiority).
Time in range as measured by CGM with glucose of 70 mg/dL to 180 mg/dL was 52% for the technosphere insulin group and 51% with usual care at 17 weeks. Time spent in hypoglycemia with a glucose of less than 70 mg/dL was also similar between the two groups at 2% with technosphere insulin and 2.1% with usual care (P = .002 for noninferiority).
No differences in diabetes distress, hypoglycemia confidence or insulin treatment satisfaction were observed between the groups. Both groups also had a similar change in body weight from baseline to 17 weeks.
At least one adverse event occurred in 77% of the technosphere insulin group and 64% of the usual care group. The most common adverse event related to technosphere insulin was cough. There was no difference in forced expiratory volume between the technosphere insulin and usual care group at 17 weeks, and no adults in the study had a reduction in forced expiratory volume of 20% or more at 17 weeks.
Researchers also presented data from a subgroup analysis examining outcomes by pre-study insulin delivery method. Of the study group, 48% were using automated insulin delivery before the study, 44% were receiving multiple daily injections and 6% were using a sensor-augmented insulin pump. HbA1c for pre-study multiple daily insulin injection and sensor-augmented pump users receiving technosphere insulin was 7.6% at 17 weeks, whereas pre-study automated insulin delivery users receiving inhaled insulin had a 7.7% HbA1c.
Time in range with pre-study multiple daily insulin injection or sensor-augmented pump users receiving technosphere insulin increased from 49% at baseline to 52% at 17 weeks. Pre-study automated insulin delivery users receiving technosphere insulin had a decline in time in range from 55% at baseline to 51% at 17 weeks, with the decrease mostly seen during nighttime.
Heterogeneity with inhaled insulin
Technosphere insulin met the trial’s noninferiority endpoint, but outcomes varied between individuals. Among the technosphere insulin group, 30% achieved an HbA1c of less than 7% at 17 weeks and 21% improved their HbA1c by 0.5 percentage points or more from baseline to 17 weeks. However, 26% of adults had 0.5 percentage point or greater increase in HbA1c.
Similar heterogeneity was seen with time in range. Of adults receiving technosphere insulin, 24% had a time in range of 70% or higher at 17 weeks and 25% improved their time in range by 10 percentage points or more from baseline to 17 weeks. However, 31% of the technosphere insulin group had their time in range decline by 10 percentage points or more from baseline to 17 weeks.
Variability was also seen in the subgroup analysis. Of adults who used multiple daily injections or sensor-augmented pump therapy before the study and received technosphere insulin, 23% improved their HbA1c by 0.5 percentage points or more from baseline to 17 weeks and 25% had a 0.5 percentage point or more increase in HbA1c. For automated insulin delivery users receiving technosphere insulin, 19% had an HbA1c improvement of 0.5 percentage points or more during the study and 30% had HbA1c worsen by 0.5 percentage points or more.
Carol J. Levy, MD, director of the Mount Sinai Diabetes Center and professor in the department of medicine and department of obstetrics, gynecology and reproductive science at Icahn School of Medicine at Mount Sinai, said the variability among people receiving technosphere insulin was much greater than that found in the usual care group.
“One size does not fit all,” Levy said during the presentation. “All of us provide care for people with diabetes, and a treatment regimen that works for one individual may not be as optimal as another.”
Tips for using inhaled insulin
The INHALE-3 trial provided lots of insight on how to best use technosphere insulin in practice, according to Thomas Blevins, MD, FACE, a clinical endocrinologist at Texas Diabetes and Endocrinology in Austin, Texas. Blevins said providers should explain the rapid effect of the insulin to patients, discuss dosing and potential adverse events and show them how to use the device and cartridges.
“The INHALE-3 study is really instructive to us as clinicians,” Blevins said. “It tells us how it works; we learn about conversions [from rapid-acting analog insulin] and we learn about best practices.”
Dosing could change from what providers were previously using. The product insert equates 1 U rapid-acting analog insulin to 1 U to 1.6 U technosphere insulin. Blevins said he has always instructed patients to take 4 U technosphere insulin for every 2 U rapid-acting analog insulin. However, Hirsch said INHALE-3 revealed the conversion rate could be higher.
“We have to be more aggressive than what is in the U.S. package insert,” Hirsch said. “We found out twofold was still underdosed and, as a rule of thumb, it was 2.5 to three times [higher] than a rapid-acting dose.”
Hirsch said using technosphere insulin may be best for people engaged in their diabetes self-management and those who want to have an alternative to insulin pump therapy. During a Q&A session, Levy added it is crucial for providers to explain technosphere insulin to patients and work with them when initiating therapy
“The most important thing is to have a discussion with the patient before you proceed with any treatment regimen,” Levy said. “You explain how this insulin works, you say what are the advantages and what are the potential considerations.”
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Akturk HK, et al. 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. Presented at: American Diabetes Association Scientific Sessions; June 21-24, 2024; Orlando.
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