Comparison of pharmacokinetics and dynamics of the long-acting insulin analogs glargine and detemir at steady state in type 1 diabetes mellitus: a double-blind, randomized, cross-over study

Objective. To compare pharmacokinetics and -dynamics (PD) of insulin glargine (GLA) and detemir (DET), 24 subjects with T1DM (38±10 years, BMI 22.4±1.6, kg/m, HbA1c 7.2±0.7%, mean±SD) were studied after 2 week treatment with either GLA or DET once daily (randomized, double-blind, cross-over study). Methods. Plasma glucose (PG) was clamped at 100 mg/dl for 24-h after s.c. injection of 0.35 U/kg. Primary endpoint was end of action (time at which PG was >150 mg/dl). Results. With GLA, PG remained at 103±3.6 mg/dl up to 24 h (all subjects completed the study). PG increased progressively after 16 h with DET, and only 8 subjects (33%) completed the study with PG <180 mg/dl. Glucose infusion rate (GIR) was similar with DET and GLA for 12 h, after which it decreased more rapidly with DET (p<0.001). Estimated total insulin activity (GIR-AUC0-end of GIR) was 1412±662 and 915±225 mg/Kg (GLA vs DET, p<0.05), with median time of end of action 24 h and 17.5 h (GLA and DET, p<0.001). Antilipolytic action of DET was lower than that of GLA (AUC free fatty acids0-24 =11±1.7 vs 8±2.8 mmol/l, respectively, p<0.001). Conclusions. DET has effects similar to GLA during initial 12 h, but lower during 12-24 h. Abbreviations: PK, pharmacokinetics; PD, pharmacodynamics; T1DM, type 1 diabetes Mellitus; GIR, glucose infusion rate