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

Juliana Bue-Valleskey; Leslie Klaff; Jang Ik Cho; Mary Anne Dellva; Nanette C Schloot; Janet Tobian; Junnosuke Miura; Dominik Dahl

doi:10.1007/s13300-020-00987-8

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

Diabetes Ther. 2021 Feb;12(2):569-580. doi: 10.1007/s13300-020-00987-8. Epub 2021 Jan 17.

Authors

Juliana Bue-Valleskey¹, Leslie Klaff², Jang Ik Cho³, Mary Anne Dellva³, Nanette C Schloot⁴, Janet Tobian³, Junnosuke Miura⁵, Dominik Dahl⁶

Affiliations

¹ Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA. bue-valleskey_juliana_m@lilly.com.
² Rainier Clinical Research Center, Renton, WA, USA.
³ Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
⁴ Lilly Deutschland GmbH, Bad Homburg, Germany.
⁵ Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
⁶ Gemeinschaftspraxis fur Innere Medizin und Diabetologie, Hamburg, Germany.

Abstract

Introduction: The 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.

Methods: In 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.

Results: HbA1c 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.

Conclusion: Overall 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 registration: ClinicalTrials.gov, NCT03214367.

Keywords: Lispro; Type 1 diabetes; Ultra rapid lispro.

Associated data

ClinicalTrials.gov/NCT03214367