The novel long-acting insulin LY2605541 is superior to insulin glargine in lowering intra-day glucose variability and hypoglycemia event rate from Continuous Glucose Monitoring (CGM) in patients with type 2 diabetes*

Objectives: The basal insulin analog LY2605541 (LY) is PEGylated insulin lispro with a large hydrodynamic size which delays insulin absorption and reduces clearance, resulting in prolonged duration of action. Methodology: Hypoglycemia and glucose variability were assessed with CGM of interstitial glucose (IG) in a subset of patients from a Phase 2, randomized, open-label, parallel study of LY (n = 51) or insulin glargine (GL, n = 25). CGM was conducted on 3 consecutive days (72 – 84 hrs) during the week before Week 0, 6, and 12 study visits. IG intra-patient intra- and inter-day standard deviations (SD) during nocturnal (2400 – 0600 hrs) and diurnal (0600 – 2400 hrs) periods were calculated to assess glucose variability. A hypoglycemia episode was defined as IG ≤70 mg/dL and continued for 15 min (or 3 time points) until IG > 70 mg/dL. All statistical comparisons were tested at 2-sided alpha = 0.1. Results: At 12 weeks, LY-treated patients spent less time with IG below 70 mg/dL than GL-treated patients during the nocturnal period (11 ± 5 v 38 ± 13 min, p = 0.024) and during the 24-hr period (25 ± 6 v 83 ± 16 min, p < 0.001). Significantly fewer LY- than GL-treated patients experienced any hypoglycemia (50.0% v 78.3%, p = 0.036), including nocturnal hypoglycemia (20.5% v 47.8%, p = 0.027), based on CGM. At 12 weeks, both treatments resulted in similar mean glucose values, as indicated by the area under the IG curve, during the 24-hr period (LY: 11601 mmol/L·min; GL: 11286 mmol/L·min). LY-treated patients had significantly lower intra-day glucose SD at 12 weeks compared to GL-treated patients for both nocturnal (1.00 ± 0.07 v 1.35 ± 0.16 mmol/L, p = 0.061) and diurnal (2.03 ± 0.10 v 2.50 ± 0.18 mmol/L, p = 0.039) periods. Conclusions: In conclusion, by CGM, LY treatment compared to GL resulted in: less time spent in hypoglycemia, fewer patients experiencing hypoglycemia, and lower intra-day glucose variability. Reference of the Encore