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

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), 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. 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 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). 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.