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.

Abstract

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). Subjects with T1D (<i>N</i> = 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), naïve 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. 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 β-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). 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.