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

• DOI: 10.2337/figshare.13103027.v1
• Publication Date: 2020-11-10T18:12:14Z
• Authors: Paola Lucidi; Paola Candeloro; Patrizia Cioli; Anna Marinelli An...; Chiara Pascucci; Angela Gambelunghe; Geremia B. Bolli; Carmine G. Fanelli; Francesca Porcellati
• Keywords: Pharmacokinetic, Pharmacodynamic; Clinical; Equivalent Doses, Insulin Glargine, Insulin Degludec; Type 1 Diabetes; 3. Good health

<b>OBJECTIVE</b>

<p><b> </b></p>

<p>To prove equivalence of individual, clinically-titrated basal insulin doses of Gla-300 and Deg-100 under steady-state conditions in a single-blind, randomized, crossover study, on the glucodynamics (PD) in people with type 1 diabetes (T1DM).</p>

<p><b>RESEARCH DESIGN AND METHODS</b></p>

<p>T1DM subjects [N=22, 11 males M, age 44.3±12.4 years, disease duration 25.5±11.7 years, A1C 7.07±0.63% (53.7±6.9 mmol/mol), BMI 22.5±2.7 kg/m²], naïve to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34±0.08 U.Kg^-1) and <a>Deg-100 </a>(0.26±0.06 U.Kg^-1), (dosing at 20.00h), after 3 months of optimal titration of basal (and bolus) insulin.</p>

<p><b>RESULTS</b></p>

<p>At the end of 3 months, Gla-300 and Deg-100 reduced slightly and similarly A1C vs baseline. Clamp average plasma glucose (0-24h) was euglycemic with both insulins. The area under curve of glucose infused [AUC-GIR_(0-24h)] was equivalent for the two insulins (ratio 1.04, 90% CIs 0.91, 1.18). Suppression of endogenous glucose production, free fatty acids (FFA), glycerol and b-hydroxybutyrate was 9%, 14%, 14% and 18% greater respectively, with Gla-300 as 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 vs Deg-100 (ratio 0.77, 90% CI 0.63, 0.92).</p>

<p><b>CONCLUSIONS</b></p>

<p>In T1DM, 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 as compared with Deg-100 are higher, and associated with quite similar even 24h distribution of PD and anti-lipolytic effects.</p>