104-LB: Assessing Infusion Site Reactions with URLi in Continuous Subcutaneous Insulin Infusion

Background: In phase 3 trials, ultra rapid lispro (URLi) showed superior postprandial glucose control and non-inferior HbA1c reduction compared to Humalog® (Lispro). However, infusion site reactions (combined; ISRs) were more frequent with URLi. Methods: We examined whether occurrence of ISRs was related to any intrinsic or extrinsic factors by analyzing data from the 16-week PRONTO-Pump-2 trial in patients with T1D (URLi, N=215; Humalog, N=217) between randomization and end of treatment period. Results: The most frequently reported adverse events (AEs) were infusion site reaction (URLi, n=41 [19.1%]; Humalog, n=15 [6.9%]) and infusion site pain (URLi, n=34 [15.8%]; Humalog, n=6 [2.8%]). ISRs were reported by 37.7% of patients on URLi and 10.1% on Humalog. Most ISRs with URLi started in the first 4 weeks after randomization, were primarily mild in severity (~76%) and lasted a median of 2-6 days, depending on the type of reaction. Individual ISRs resolved during the study, but another event could occur with a different infusion set/site. Overall, 7 (3.3%) patients discontinued URLi treatment due to ISRs, 6 within the first 4 weeks after randomization and 1 at week 6. Gender, age, BMI, ethnicity, race, infusion set model, bolus speed, total daily dose, duration of diabetes and duration of insulin pump use did not impact incidence of ISRs between treatments. However, significant treatment-by-subgroup interactions were observed for cannula length (6mm vs. >6mm; p=0.070) and region (US vs. non-US; p=0.046): incidence of ISRs with cannula length >6mm and incidence of ISRs in US was similar between treatments, but a higher incidence of ISRs was observed with URLi when cannula length was 6 mm or in non-US regions. Conclusions: Infusion site reaction and infusion site pain were the most frequently reported AEs, although most were mild and resolved in less than a week. Differential treatment effects on ISR occurrence were seen with cannula length or region. Further studies are needed to confirm these findings. Disclosure D. A. Ignaut: Employee; Self; Eli Lilly and Company. J. Cho: None. J. C. Elpers: Employee; Self; Eli Lilly and Company. F. B. Chigutsa: None. C. Piras de Oliveira: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company