Long-term Efficacy and Safety of Ultra Rapid Lispro in Japanese Patients With Type 1 Diabetes: Subpopulation Analysis of the 52-Week PRONTO-T1D Study.

ABSTRACT

INTRODUCTION: The PRONTO-T1D study evaluated the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes mellitus. After 26 weeks of treatment, mealtime and postmeal URLi provided effective and comparable glycemic control in a prespecified subpopulation analysis of Japanese patients from PRONTO-T1D. We present the results of a 52-week study which evaluated the long-term efficacy and safety of URLi in Japanese patients. METHODS: After an 8-week lead-in period to optimize basal insulin treatment, Japanese patients were randomized to one of three treatment groups the 52-week double-blind mealtime URLi (n = 62) or mealtime lispro (n = 59) group, respectively, or the 52-week open-label postmeal URLi (n = 46) group. RESULTS: At week 52, there were no statistically significant differences in change from baseline in hemoglobin A1c (HbA1c) between Japanese patients on URLi and those on lispro; the least-squares mean (LSM) treatment difference was 0.04% (95% confidence interval [CI] - 0.18, 0.25) between mealtime URLi and lispro, and 0.04% (95% CI - 0.19, 0.28) between postmeal URLi and mealtime lispro. No significant between-group differences were observed in the number of patients achieving the HbA1c target of < 7.0% (20.0, 30.5 and 16.3% of those on mealtime URLi, mealtime lispro and postmeal URLi, respectively). Daily average blood glucose levels in the 10-point self-monitored blood glucose profiles at week 52 were similar between treatments. However, compared with lispro, lower blood glucose levels were observed for the mealtime URLi group at the morning 1- and 2-h postmeal time points with LSM differences of - 32.7 mg/dL (- 1.82 mmol/L) (p = 0.005) and - 23.2 mg/dL (- 1.29 mmol/L) (p = 0.029), respectively. There were no significant treatment differences in the incidences of treatment-emergent adverse events, documented hypoglycemia and severe hypoglycemia; however, the rate of documented hypoglycemia was lower in the mealtime URLi arm compared with the lispro arm. CONCLUSIONS: Overall glycemic control and improved postprandial glucose via self-monitoring was maintained in Japanese patients following 52 weeks of treatment with URLi versus lispro, including postmeal URLi administration. TRIAL REGISTRATION ClinicalTrials.gov NCT03214367.