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: 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?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. CONCLUSIONS:The 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.

SUBMITTER: Klaff L 

PROVIDER: S-EPMC7539952 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature