Improved Postprandial Glucose with Inhaled Technosphere Insulin Compared with Insulin Aspart in Patients with Type 1 Diabetes on Multiple Daily Injections: The STAT Study

Background: The majority of therapies have generally targeted fasting glucose control, and current mealtime insulin therapies have longer time action profiles than that of endogenously secreted insulin. The primary purpose of this study was to assess both glucose time-in-range (TIR: 70-180mg/dL) and postprandial glucose excursions (PPGE) in 1-4h using a real-time continuous glucose monitor (CGM) with Technosphere insulin (TI) versus insulin aspart in patients with type 1 diabetes (T1DM) on multiple daily injections (MDI). Research Design and Methods: This pilot, investigator-led, collaborative, open-label, multicenter, clinical research trial enrolled 60 patients with T1DM with HbA1c levels 6.5% and 10%. Individuals were randomized to treatment with titrated TI (n=26) or titrated insulin aspart (n=34), stratified by baseline HbA1c levels (8% or >8%). All were required to wear a real-time CGM throughout the trial. All patients in the TI group were advised to take supplemental inhalations at 1 and 2h after meals if indicated based on postprandial glucose (PPG) values. The coprimary outcomes were assessed both in the full intent-to-treat population and in those individuals randomized to TI who were compliant with supplemental doses 90% of the time (n=15). The CGM data were analyzed using linear regression models. Results: Overall, those treated with TI versus aspart achieved comparable TIR, but less time spent in hypoglycemia (<60 and <50mg/dL, both P<0.05). In the TI-compliant group (n=15), TIR was significantly greater (62.5%2.6% vs. 53.8%1.7%, P=0.009) and time in hyperglycemia >180mg/dL was lower (34.2%+/- 2.7% vs. 41.0%+/- 1.7%, P=0.045) as compared with the aspart group. PPG was also significantly lower in the TI cohort at 60 and 90min postmeal, and PPGE were lower in the TI-compliant group as compared with the aspart group over 1-4-h postmeal (P<0.05). In addition, there was weight gain in the aspart group compared with weight loss in the TI group (P=0.006) despite higher prandial TI insulin dose. Conclusions: We conclude that using TI appropriately at mealtimes with supplemental dosing improves prandial glucose (TIR and 1-4h) control without any increase in time in hypoglycemia or weight gain in patients with T1DM on MDI. The study results support a larger study using a treat-to-target design to confirm these findings. Clinical trial reg. no. NCT03143816, clinicaltrials.gov.