Inhaled Technosphere Insulin Plus Insulin Degludec for Adults with Type 1 Diabetes: The INHALE-3 Extension Study

<b><i>Background:</i></b> Postmeal hyperglycemia is difficult to avoid even with automated insulin delivery (AID) due to the delayed effect of subcutaneously administered rapid-acting insulin analogs. Inhaled technosphere insulin (TI, Afrezza®) has a more rapid onset of action with the potential to reduce the postmeal glucose rise. We evaluated the effects of a regimen of TI and degludec over 30 weeks. <b><i>Methods:</i></b> In total, 123 adults with type 1 diabetes (T1D) participated in a 17-week multicenter randomized controlled trial comparing a regimen of TI plus insulin degludec versus usual care, which consisted predominantly of AID or multiple daily insulin injections (MDI). Interested participants in the TI-degludec group continued this regimen for an additional 13 weeks, with no scheduled visits prior to a final visit at 30 weeks to approximate real-world care. <b><i>Results:</i></b> Of the 62 participants in the TI-degludec group, 58 completed the 17-week visit and 45 continued into the extension phase. Prior to the study, 44% were using AID, 9% a sensor-augmented pump without automation, and 47% MDI. Mean HbA1c was 7.6% ± 1.0% at baseline, 7.6% ± 1.0% at 17 weeks, and 7.4% ± 1.0% at 30 weeks. Mean HbA1c change from 17 weeks to 30 weeks was -0.21% (95% confidence interval -0.33% to -0.09%, <i>P</i> < 0.001). HbA1c was <7.0% in 21% at baseline, 30% at 17 weeks, and 42% at 30 weeks. Mean time in range 70-180 mg/dL was 52% ± 18% at baseline, 53% ± 20% at 17 weeks, and 54% ± 20% at 30 weeks. Mean percent time <54 mg/dL was 0.4% ± 0.6%, 0.4% ± 0.8%, and 0.6% ± 1.0%, respectively. Mean total daily TI dose at 30 weeks was 53 ± 31 U/day, which was about twice the total daily rapid-acting insulin analog dose of 24 ± 12 U/day at baseline prior to switching to TI. <b><i>Conclusions:</i></b> HbA1c levels were sustained over 30 weeks using a TI-degludec regimen after switching from AID or MDI. TI should be considered an option for people with T1D.