2853-LB: Inhaled Insulin Demonstrates Earlier Completion of Total Pharmacodynamic Effect Compared with Lispro

Introduction and Objective: Standard pharmacodynamic (PD) comparisons of prandial insulins emphasize total glucose infusion rate (GIR) area under the curve (AUC), which summarizes overall effect but provides limited resolution on when that effect occurs. The objective was to analyze clamp data as cumulative percent of total PD effect by time to characterize early versus late insulin action. Methods: Clamp data from a randomized crossover study comparing inhaled Technosphere Insulin (TI) and subcutaneous insulin lispro in adults with type 1 diabetes were reviewed. TI 12 U and lispro 8 U were selected as doses closest in overall PD exposure, reflecting the higher unit relationship between TI and rapid-acting analog insulin. GIR-time profiles were normalized to each treatment’s total GIR-AUC, and cumulative PD effect was expressed as percent of total effect achieved by 60, 90, and 120 minutes. Results: By 60 minutes, TI 12 U achieved 53% of its total PD effect (47% remaining) versus 10% for lispro 8 U (90% remaining), an absolute difference +43 percentage points (pp) and 5.3-fold higher. By 90 minutes, TI cumulative effect reached 75% (25% remaining) versus 27% (73% remaining), +48 pp; 2.8-fold. By 120 minutes, TI reached 88% (12% remaining) versus 45% (55% remaining), +43 pp; 2.0-fold. This representation demonstrates that TI delivers a substantially greater proportion of its effect earlier than lispro, a pattern that is even more pronounced at lower TI doses. Conclusion: PD data as cumulative percent of total effect provides a complementary view to AUC-based summaries by making differences in the timing and completion of insulin action more apparent. TI delivered the majority of its PD effect within the first 60 minutes, consistent with its rapid onset and earlier offset. For clinicians, these data suggest that TI action is largely completed much earlier in the post-prandial period than lispro, supporting further evaluation of whether additional dosing decisions may be made sooner with less risk for insulin stacking and subsequent hypoglycemia. Disclosure K. Kaiserman: Employee; Current; MannKind Corporation. Stock/Shareholder; Current; MannKind Corporation. J. Sylvan: Employee; Current; MannKind Corporation. L. Mycue: Employee; Current; MannKind Corporation. J. Nguyen: Other - Post-Doctoral Fellow (Contractor); Current; MannKind Corporation.