Main idea: URLi was efficacious, providing superior PPG control and less time in hypoglycemia but with more frequent infusion-site reactions compared with lispro when administered by CSII.
The aim of the study was to evaluate the efficacy and safety of ultra-rapid lispro (URLi) versus lispro (Humalog®) in people with type 1 diabetes on continuous subcutaneous insulin infusion (CSII).
This was a phase 3 16-week treat-to-target study in patients randomized to double-blind URLi (N = 215) or lispro (N = 217). The primary endpoint was the change from baseline Hemoglobin A1c(HbA1c)e A1c(HbA1c) (non-inferiority margin 4.4 mmol/mol [0.4%]), with multiplicity-adjusted objectives for postprandial glucose (PPG) levels during a meal test, and time spent in the target range 70-180 mg/dL (TIR).
Results: URLi was non-inferior to lispro for change in Hemoglobin A1c(HbA1c)e A1c(HbA1c), with a least-squares mean (LSM) difference of 0.3 mmol/mol or 0.02%. URLi was superior to lispro in controlling 1- and 2-h PPG levels after the meal test: LSM difference -1.34 mmol/L (95% CI -2.00, -0.68) or -24.1 mg/dL at 1 h and -1.54 mmol/L or -27.8 mg/dL (95% CI -42.6, -13.0) at 2 h; both p < .001. TIR and time in hyperglycemia were similar between groups but URLi resulted in significantly less time in hypoglycemia (<3.0 mmol/L [54 mg/dL]) over the daytime, night-time and 24-h period: LSM difference -0.41%, -0.97% and -0.52%, respectively, all p < .05. The incidence of treatment-emergent adverse events was higher with URLi (60.5% vs. 44.7%), driven by infusion-site reaction and infusion-site pain, which was mostly mild or moderate. Rates of severe hypoglycemia and diabetic ketoacidosis were similar between groups.