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

Abstract

AimsTo 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 methodsAfter 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.ResultsBoth 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 < 0.001). The rate and incidence of severe, documented and postprandial hypoglycaemia (<3.0 mmol/L) was similar between treatments, but mealtime URLi demonstrated a 37% lower rate in the period >4 hours after meals (P = 0.013). Injection site reactions were reported by 2.9% of patients on mealtime URLi, 2.4% on post‐meal URLi, and 0.2% on lispro. Overall, the incidence of treatment‐emergent adverse events was similar between treatments.ConclusionsThe results showed that URLi provided good glycaemic control, with non‐inferiority to lispro confirmed for both mealtime and post‐meal URLi, while superior PPG control was demonstrated with mealtime dosing.