Pharmacokinetic and Pharmacodynamic Head-to-Head Comparison of Clinical, Equivalent Doses of Insulin Glargine 300 units . mL-1 and Insulin Degludec 100 units . mL-1 in Type 1 Diabetes

OBJECTIVE To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units . mL(-1) (Gla-300) and degludec 100 units . mL(-1) (Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Subjects with T1D (N = 22, 11 men, age 44.3 +/- 12.4 years, disease duration 25.5 +/- 11.7 years, A1C 7.07 +/- 0.63% [53.7 +/- 6.9 mmol . mL(-1)], BMI 22.5 +/- 2.7 kg . m(-2)), naive to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34 +/- 0.08 units . kg(-1)) and Deg-100 (0.26 +/- 0.06 units . kg(-1)), dosing at 2000 h, after 3 months of optimal titration of basal (and bolus) insulin. RESULTS At the end of 3 months, Gla-300 and Deg-100 reduced slightly and, similarly, A1C versus baseline. Clamp average plasma glucose (0-24 h) was euglycemic with both insulins. The area under curve of glucose infused (AUC-GIR([0-24 h])) was equivalent for the two insulins (ratio 1.04, 90% CI 0.91-1.18). Suppression of endogenous glucose production, free fatty acids, glycerol, and beta-hydroxybutyrate was 9%, 14%, 14%, and 18% greater, respectively, with Gla-300 compared with Deg-100 during the first 12 h, while glucagon suppression was no different. Relative within-day PD variability was 23% lower with Gla-300 versus Deg-100 (ratio 0.77, 90% CI 0.63-0.92). CONCLUSIONS In T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects.