1740-P: Inhaled Insulin Demonstrates Lower Variability and Faster Onset Compared with Subcutaneous Rapid-Acting Analogs

Introduction and Objective: Inhaled Technosphere Insulin (TI) is an ultra rapid-acting insulin requiring individualized titration to reach glycemic goals. Subcutaneous insulin therapy can be described in units/kg (U/kg) to approximate daily insulin needs. Because TI has a different time-action profile than subcutaneous rapid-acting analog (RAA) insulin, it may require unique replacement needs. This analysis aimed to examine TI and usual care (UC) dose distributions in U/kg and whether higher U/kg dosing may demonstrate potential benefits with TI compared to UC. Methods: Adults with type 1 diabetes (T1D) enrolled in INHALE-3 and randomized to TI completed two standardized 120-min meal challenges: (1) an initial meal using TI dosed based on conversion from their RAA; and (2) the same meal after 17 weeks of TI titration. Participants randomized to UC completed the same meal challenge using their RAA regimen. All meal challenge doses were categorized into high vs low based on median U/kg. Median titrated TI dose defined TI-low and TI-high; UC was divided into UC-low and UC-high by its own U/kg distribution. Results: Mean glucose excursion was significantly lower for TI-high compared to UC-high from 30-120 mins (p<0.05). TI-high also demonstrated lower excursion than TI-low (p<0.05). No statistical difference was observed between UC-low and UC-high, nor between TI-low and UC-low. Mean U/kg were: TI-low 0.074, TI-high 0.16; UC-low 0.042, UC-high 0.084. Conclusion: TI titration over 17 weeks resulted in higher individualized U/kg dosing and may better reflect real-world postprandial insulin needs. Across strata, TI-low performed similarly to UC, indicating that under-dosing TI yields comparable glycemic outcomes to standard therapies. In contrast, TI-high demonstrated significantly improved postprandial excursions, suggesting that some individuals may require higher U/kg TI dosing for optimal meal coverage. These findings highlight the need for further evaluation of individualized TI dose optimization in T1D management. Disclosure J.T. Rittenberry: Employee; Current; MannKind Corporation. J. Sylvan: Employee; Current; MannKind Corporation. L.E. Mycue: Employee; Current; MannKind Corporation. J.K. Rinker: Employee; Current; MannKind Corporation. J. Nguyen: Other - Post-Doctoral Fellow (Contractor); Current; MannKind Corporation. K. Kaiserman: Employee; Current; MannKind Corporation. Stock/Shareholder; Current; MannKind Corporation.