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 < 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. 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.

Ultra-Rapid Lispro Efficacy and Safety Compared to Humalog® in Japanese Patients with Type 1 Diabetes: PRONTO-T1D Subpopulation Analysis

“…PRONTO-T1D demonstrated that mealtime and postmeal URLi are non-inferior to lispro in terms of change in HbA1c following 26 weeks of treatment [21]. In addition, mealtime URLi was superior to lispro at reducing 1-and 2-h PPG excursions during the meal test [21].…”

“…The analyses have already been described for the overall population [21]. These methods were applied to the Japanese population in a pre-specified subset analysis, although statistical power was not taken into consideration, and p values are provided as a reference.…”

“…The primary study endpoint was the change in HbA1c from baseline to week 26. For the overall population, non-inferiority of both mealtime and postmeal URLi to lispro was confirmed by the change from baseline to week 26 in HbA1c [21] (the upper 95% confidence interval [CI] of LSM difference was lower than 0.4%, defined as the pre-specified non-inferiority criteria for the overall population).…”

“…PRONTO-T1D compared double-blind mealtime URLi to lispro with an open-label postprandial URLi treatment group in combination with insulin glargine or insulin degludec. This pivotal study demonstrated that URLi was non-inferior to lispro for change in HbA1c following 26 weeks of treatment [21]. In a recent survey, Japanese patients with diabetes reported moderate to severe burden in multiple aspects of their lives associated with current mealtime insulin timing [22].…”

“…PRONTO-T1D was a recent, prospective, randomized, double-blind, phase 3 trial in adults with T1DM [21]. PRONTO-T1D compared double-blind mealtime URLi to lispro with an open-label postprandial URLi treatment group in combination with insulin glargine or insulin degludec.…”