Morning administration of 0.4 U/kg/day insulin glargine 300 U/mL provides less fluctuating 24-hour pharmacodynamics and more even pharmacokinetic profiles compared with insulin degludec 100 U/mL in type 1 diabetes

Aim To compare steady state pharmacodynamic and pharmacokinetic profiles of insulin glargine 300 U/mL (Gla-300) with insulin degludec 100 U/mL (Deg-100) in people with type 1 diabetes. Methods This single-centre, randomized, double-blind crossover euglycaemic clamp study included two parallel cohorts with fixed once-daily morning dose regimens. For both insulins participants received 0.4 ( n = 24) or 0.6 U/kg/day ( n = 24), before breakfast, for 8 days prior to the clamp. The main endpoint was within-day variability (fluctuation) of the smoothed glucose infusion rate (GIR) over 24 hours (GIR-smFL 0–24 ). Results Gla-300 provided 20% less fluctuation of steady state glucose infusion rate profiles than Deg-100 over 24 hours at 0.4 U/kg/day (GIR-smFL 0–24 treatment ratio 0.80 [90% confidence interval: 0.66 to 0.96], P = 0.047), while at the dose of 0.6 U/kg/day the difference between insulins was not statistically significant (treatment ratio 0.96 [0.83 to 1.11], P = 0.603). Serum insulin concentrations appeared more evenly distributed with both dose levels of Gla-300 versus the same doses of Deg-100, as assessed by relative 6-hour fractions of the area under the curve within 24 hours. Both insulins provided exposure and activity until 30 hours (end of clamp). Conclusion Gla-300 provides less fluctuating steady state pharmacodynamic profiles (i.e. lower within-day variability) and more evenly distributed pharmacokinetic profiles, compared with Deg-100 in a once-daily morning dosing regimen of 0.4 U/kg/day.