OBJECTIVE -To compare pharmacokinetics and pharmacodynamics of insulin analogs glargine and detemir, 24 subjects with type 1 diabetes (aged 38 Ϯ 10 years, BMI 22.4 Ϯ 1.6 kg/m 2 , and A1C 7.2 Ϯ 0.7%) were studied after a 2-week treatment with either glargine or detemir once daily (randomized, double-blind, crossover study).RESEARCH DESIGN AND METHODS -Plasma glucose was clamped at 100 mg/dl for 24 h after subcutaneous injection of 0.35 unit/kg. The primary end point was end of action (time at which plasma glucose was Ͼ150 mg/dl).RESULTS -With glargine, plasma glucose remained at 103 Ϯ 3.6 mg/dl up to 24 h, and all subjects completed the study. Plasma glucose increased progressively after 16 h with detemir, and only eight subjects (33%) completed the study with plasma glucose Ͻ180 mg/dl. Glucose infusion rate (GIR) was similar with detemir and glargine for 12 h, after which it decreased more rapidly with detemir (P Ͻ 0.001). Estimated total insulin activity (GIR area under the curve [AUC] 0 -end of GIR ) was 1,412 Ϯ 662 and 915 Ϯ 225 mg/kg (glargine vs. detemir, P Ͻ 0.05), with median time of end of action at 24 and 17.5 h (glargine vs. detemir, P Ͻ 0.001). The antilipolytic action of detemir was lower than that of glargine (AUC free fatty acids 0 -24 h 11 Ϯ 1.7 vs. 8 Ϯ 2.8 mmol/l, respectively, P Ͻ 0.001).CONCLUSIONS -Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h.

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