Work

Ultra-Rapid Lispro Has an Improved Pharmacokinetic Profile for Exercise Compared With Lispro, Resulting in Less Exercise-Associated Hypoglycemia in Adults With Type 1 Diabetes on Open-Loop Continuous Subcutaneous Insulin Infusion

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: OBJECTIVE: To compare the glycemic response and pharmacokinetics (PK) of ultra-rapid lispro (URLi) versus lispro during manual basal rate reductions (BRRs) before exercise with conventional continuous subcutaneous insulin infusion (CSII) in active adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: This study was a double-blind, four-period, crossover, randomized controlled trial. Exercise (60 min walking at 45-55% VO2max) was performed 4 h after a standardized meal, with either a 50% (-60 min) or 100% (-15 min) BRR before exercise using URLi or lispro. The primary end point was the change in glucose during exercise, and insulin lispro PK was the secondary end point. RESULTS: Twenty-five participants (mean ± SD age 36.7 ± 10.3 years; mean ± SD HbA1c 50.4 ± 8.5 mmol/mol [6.76 ± 0.8%]; 48% female) completed the study. URLi significantly attenuated the reduction in glucose level compared with lispro during both the 50% BRR (-26.8 ± 37 vs. -39.0 ± 39 mg/dL; P < 0.05) and the 100% BRR (-46.9 ± 32 vs. -60.5 ± 39 mg/dL; P < 0.01). Circulating insulin lispro concentrations rose in the first 15 min of exercise, but maximum concentration was lower with URLi versus lispro within each BRR strategy. Numerically less hypoglycemia was observed during exercise with URLi (6%) compared with lispro (16%). Following a postexercise meal, faster insulin absorption of URLi resulted in an earlier postprandial glucose lowering compared with lispro. CONCLUSIONS: Using URLi in conventional CSII pump therapy provides more effective BRRs prior to exercise compared with lispro, with fewer hypoglycemic events in active adults with type 1 diabetes.

Source: Diabetes Care

DOI: 10.2337/dc25-2294