Compatibility and Safety of Ultra Rapid Lispro with Continuous Subcutaneous Insulin Infusion in Patients With Type 1 Diabetes: PRONTO-Pump Study.

Background Ultra rapid lispro (URLi) is a new insulin lispro formulation that has accelerated absorption and improved postprandial glucose control compared to insulin lispro (Humalog®). The compatibility and safety of URLi versus lispro were evaluated in patients with type 1 diabetes using continuous subcutaneous insulin infusion (CSII, insulin pump). Methods In this Phase 3, double-blind, crossover study, 49 patients were randomized to two 6-week treatment periods, following a 2-week lead-in period on lispro. Primary endpoint was the rate of infusion set failures due to a pump occlusion alarm, or unexplained hyperglycemia with blood glucose >13.9 mmol/L (250 mg/dL) that did not decrease within 1 hour following a correction bolus. Results There was no significant difference in the rate of infusion set failures between URLi and lispro (0.03 versus 0.05 events/30 days, p=0.375). A higher rate of premature infusion set changes was observed with URLi (1.13 versus 0.78 events/30 days; p=0.028), translating to 1 additional infusion set change approximately every 3 months. A trend toward improved glycemic control was observed with URLi treatment: time in range 3.9-10.0 mmol/L (71-180 mg/dL) was 65.7%±1.3% versus 63.0%±1.3%. Treatment-emergent adverse events (TEAEs) were reported by 46.9% of patients on URLi treatment and 18.8% on lispro. This difference was driven by an increase in infusion site reactions - over 90% were mild. Incidence of all other TEAEs and severe hypoglycemia was similar between treatments. Conclusions URLi was compatible with insulin pump use with a safety profile similar to lispro.