Long-Term Efficacy and Safety of Ultra Rapid Lispro (URLi) in Adults with Type?1 Diabetes: The PRONTO-T1D Extension

摘要

IntroductionThe PRONTO-T1D study, which evaluated the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type?1 diabetes (T1D), met the primary endpoint of noninferiority of HbA1c change from baseline compared to lispro at 26?weeks. We present results of an additional 26-week treatment phase evaluating long-term efficacy and safety of URLi.MethodsIn this phase?3, treat-to-target study, subjects were randomized to double-blind mealtime URLi, lispro, or open-label postmeal URLi with insulin degludec or glargine for 26?weeks. Subjects in the double-blind URLi ( n =?451) and lispro ( n =?442) groups continued for another 26?weeks to assess long-term efficacy and safety.ResultsHbA1c increased marginally during the long-term maintenance period (week?26–52) in both groups to 7.47% (URLi) and 7.54% (lispro). At week?52, there were no statistically significant treatment differences in change from baseline HbA1c with a least-squares mean treatment difference (95% confidence interval) of ? 0.06% (? 0.16, 0.03). Proportions of patients with HbA 1c ??7% at week?52 were similar (URLi, 26.8%; lispro, 24.5%). Self-monitored blood glucose (SMBG) showed that 1-h (9.23 versus 10.14?mmol/L) and 2-h (8.40 versus 9.53?mmol/L) postmeal daily mean glucose was statistically significantly ( p ?0.001) lower with URLi than lispro. The rate and incidence of severe, documented, and postprandial hypoglycemia (?54?mg/dl [3.0?mmol/L]) were similar between treatments, but URLi demonstrated a 31% lower rate in the period more than 4?h after meals, ( p =?0.023). Injection site reactions were reported by 3.3% of patients on URLi and 0.9% on lispro. The incidence of treatment-emergent adverse events was similar between treatments.ConclusionOverall glycemic control and improved postprandial glucose via SMBG were maintained after 52?weeks with URLi versus lispro, suggesting that the efficacy of URLi is preserved during long-term treatment in patients with T1D. No long-term safety issues were identified with URLi.Trial RegistrationClinicalTrials.gov, NCT03214367.