Lower Pharmacokinetic and Pharmacodynamic Within-Day Variability of Individual Clinical Doses of Insulin Glargine 300 U/ml vs. Glargine 100 U/ml in T1DM

Previous studies have examined variability of pharmacokinetics (PK, plasma insulin concentration) and pharmacodynamics (PD, glucose infusion rate, GIR) of basal insulins at steady-state (SS) and at fixed doses in all subjects studied. To establish within-day PK/PD variability of individual, different, doses of insulin Glargine 300 U/ml (Gla-300) vs. Glargine 100 U/ml (Gla-100) that people with T1DM use in real life. Eighteen T1DMs [age 40±11 years, diabetes duration 26±12 years, BMI 23.4±2.1 kg/m 2 , A1C 7.2±0.5% (55±6 mmol/mol)] were studied after 3 month treatment with Gla-300 and Gla-100 titrated to fasting euglycemia, with a 24 h euglycemic clamp (randomized, crossover). The individual basal insulin doses that subjects used (0.35±0.Gla-300, 0.28±0.07 Gla-100, U/kg) were injected s.c. in the clamp study. Prior to clamp, glycemic control was comparable with Gla-300 and Gla-100. In the clamp, the individual doses of Gla-300 and Gla-100 resulted in 24 h PK/PD bioequivalence, but in lower variability indices of PK/PD with Gla-300 vs. Gla-100 (Table). In conclusion, at clinical, individual doses used by T1DMs in real life, Gla-300 has lower PK/PD within-day variability vs. Gla-100. These results may explain the lower glycemic variability and lower risk for hypoglycaemia reported in clinical studies with Gla-300 vs. Gla-100. Disclosure C. Fanelli: Advisory Panel; Self; Sanofi. Other Relationship; Self; Menarini Group. P. Lucidi: Other Relationship; Self; Abbott, Menarini Group, Sanofi-Aventis. P. Candeloro: None. P. Cioli: None. A. Marinelli Andreoli: None. G.B. Bolli: Speaker9s Bureau; Self; Menarini Group, Sanofi. Research Support; Self; Sanofi. F. Porcellati: Advisory Panel; Self; Sanofi. Board Member; Self; Sanofi. Other Relationship; Self; Medtronic. Board Member; Self; Eli Lilly and Company.