T S Bailey1, J Pettus2, R Roussel3, W Schmider4, M Maroccia5, N Nassr4, O Klein6, G B Bolli7, R Dahmen4. 1. AMCR Institute, 625 West Citracado Parkway Suite 112, Escondido, California 92025, USA. Electronic address: tbailey@amcrinstitute.com. 2. University of California, San Diego, CA, USA. 3. Inserm U1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France; Diabetology, Endocrinology and Nutrition Department, DHU FIRE, Hôpital Bichat, AP-HP, 75018 Paris, France. 4. Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. 5. Umanis, Levallois-Perret, 92300 France. 6. Profil, Neuss, Germany. 7. Department of Medicine, University of Perugia Medical School, Perugia, Italy.
Abstract
AIM: To compare steady state pharmacodynamic and pharmacokinetic profiles of insulin glargine 300U/mL (Gla-300) with insulin degludec 100U/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 0.6U/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-smFL0-24). RESULTS: Gla-300 provided 20% less fluctuation of steady state glucose infusion rate profiles than Deg-100 over 24 hours at 0.4U/kg/day (GIR-smFL0-24 treatment ratio 0.80 [90% confidence interval: 0.66 to 0.96], P=0.047), while at the dose of 0.6U/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 0.4U/kg/day.
RCT Entities:
AIM: To compare steady state pharmacodynamic and pharmacokinetic profiles of insulin glargine 300U/mL (Gla-300) with insulin degludec 100U/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 0.6U/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-smFL0-24). RESULTS:Gla-300 provided 20% less fluctuation of steady state glucose infusion rate profiles than Deg-100 over 24 hours at 0.4U/kg/day (GIR-smFL0-24 treatment ratio 0.80 [90% confidence interval: 0.66 to 0.96], P=0.047), while at the dose of 0.6U/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 0.4U/kg/day.
Authors: Florentino Carral San Laureano; Mariana Tomé Fernández-Ladreda; Ana Isabel Jiménez Millán; Concepción García Calzado; María Del Carmen Ayala Ortega Journal: J Investig Med Date: 2021-03-26 Impact factor: 2.895
Authors: Andrea C Tricco; Huda M Ashoor; Jesmin Antony; Zachary Bouck; Myanca Rodrigues; Ba' Pham; Paul A Khan; Vera Nincic; Nazia Darvesh; Fatemeh Yazdi; Marco Ghassemi; John D Ivory; Areti Angeliki Veroniki; Catherine H Yu; Lorenzo Moja; Sharon E Straus Journal: J Gen Intern Med Date: 2021-03-19 Impact factor: 6.473