Ultrarapid Lispro (Lyumjev) Has an Improved Pharmacokinetic Profile for Exercise Compared With Humalog, Resulting in Less Exercise-Associated Hypoglycemia in Adults With Type 1 Diabetes on Open-Loop Continuous Subcutaneous Insulin Infusion.

Abstract

To compare the glycemic response and pharmacokinetics (PK) of Lyumjev versus Humalog during manual basal rate reductions (BRRs) before exercise with conventional continuous subcutaneous insulin infusion (CSII) in active adults with type 1 diabetes. 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 Lyumjev or Humalog. The primary endpoint was the change in glucose during exercise, and insulin lispro PK was the secondary endpoint. 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. Lyumjev significantly attenuated the reduction in glucose level compared with Humalog 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 Lyumjev versus Humalog within each BRR strategy. Numerically less hypoglycemia was observed during exercise with Lyumjev (6%) compared with Humalog (16%). Following a postexercise meal, faster insulin absorption of Lyumjev resulted in an earlier postprandial glucose lowering compared with Humalog. Using Lyumjev in conventional CSII pump therapy provides more effective BRRs prior to exercise compared with Humalog, with fewer hypoglycemic events in active adults with type 1 diabetes.