1. Evaluation of Insulin Lispro Pharmacokinetics and Pharmacodynamics Over 10 Days of Continuous Insulin Infusion in People With Type 1 Diabetes.
- Author
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Garhyan P, Pratt E, Klein O, Famulla S, Zijlstra E, Lalonde A, Swinney M, Kazda C, and Dassau E
- Subjects
- Adult, Humans, Insulin Lispro, Hypoglycemic Agents, Cross-Over Studies, Meloxicam, Blood Glucose, Insulin, Regular, Human, Insulin, Diabetes Mellitus, Type 1 drug therapy
- Abstract
Background: We evaluated the effect of meloxicam on insulin lispro pharmacokinetics and glucose pharmacodynamics over 10 days of continuous subcutaneous insulin infusion (CSII) at one infusion site in people with type 1 diabetes (T1D)., Method: This phase 1, randomized, double-blind, single-center, two-way crossover study enrolled adults with T1D for ≥1 year on stable CSII for ≥3 months. Participants randomly received U100 insulin lispro and LY900027 (U100 insulin lispro + 0.25 mg/mL meloxicam). Primary end points were area under the insulin lispro curve from 0 to 5 hours (AUC
Ins.0-5h ) after bolus administration prior to a mixed-meal tolerance test (MMTT) and maximum observed concentration of insulin lispro (CIns.max ) on days 5, 7, and 10, versus day 3 (baseline)., Results: A total of 20 participants were randomized. Insulin absorption was accelerated for insulin lispro and LY900027 from days 1 to 7. The AUCIns.0-5h was significantly lower on day 10 versus day 3 for LY900027 (-19%) and insulin lispro (-14%); the AUCIns.0-5h did not differ significantly between treatments. The CIns.max increased with LY900027 and insulin lispro (by ~14%-23% and ~16%-51%) on days 5, 7, and 10 versus day 3. The CIns.max of LY900027 was ~14%-23% lower than insulin lispro CIns.max on days 7 and 10 ( P ≤ .0805). Accelerated insulin absorption and a modest loss of total insulin exposure led to a loss of MMTT glycemic control at later time points., Conclusions: The pharmacokinetics of insulin changed over catheter wear time even when an anti-inflammatory agent was present. Postprandial glycemic control was adversely affected by the accelerated insulin absorption and decreased insulin exposure.- Published
- 2023
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