Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26‐week PRONTO‐T1D study

Aims To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes in a 26‐week, treat‐to‐target, phase 3 trial. Materials and methods After an 8‐week lead‐in to optimize basal insulin glargine or degludec, patients were randomized to double‐blind mealtime URLi (n = 451) or lispro (n = 442), or open‐label post‐meal URLi (n = 329). The primary endpoint was change from baseline glycated haemoglobin (HbA1c) to 26 weeks (non‐inferiority margin 0.4%), with multiplicity‐adjusted objectives for postprandial glucose (PPG) excursions after a meal test. Results Both mealtime and post‐meal URLi demonstrated non‐inferiority to lispro for HbA1c: estimated treatment difference (ETD) for mealtime URLi −0.08% [95% confidence interval (CI) −0.16, 0.00] and for post‐meal URLi +0.13% (95% CI 0.04, 0.22), with a significantly higher endpoint HbA1c for post‐meal URLi versus lispro (P = 0.003). Mealtime URLi was superior to lispro in reducing 1‐ and 2‐hour PPG excursions during the meal test: ETD −1.55 mmol/L (95% CI −1.96, −1.14) at 1 hour and − 1.73 mmol/L (95% CI −2.28, −1.18) at 2 hours (both P