Pharmacokinetics and Pharmacodynamics of Therapeutic Doses of Basal Insulins NPH, Glargine, and Detemir After 1 Week of Daily Administration at Bedtime in Type 2 Diabetic Subjects

Abstract

OBJECTIVE: To compare the pharmacokinetics and pharmacodynamics of NPH, glargine, and detemir insulins in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: This study used a single-blind, three-way, cross-over design. A total of 18 type 2 diabetic subjects underwent a euglycemic clamp for 32 h after a subcutaneous injection of 0.4 units/kg at 2200 h of either NPH, glargine, or detemir after 1 week of bedtime treatment with each insulin. RESULTS: The glucose infusion rate area under the curve0–32 h was greater for glargine than for detemir and NPH (1,538 ± 688; 1,081 ± 785; and 1,170 ± 703 mg/kg, respectively; P < 0.05). Glargine suppressed endogenous glucose production more than detemir (P < 0.05) and similarly to NPH (P = 0.16). Glucagon, C-peptide, free fatty acids, and β-hydroxy-butyrate were more suppressed with glargine than detemir. All 18 subjects completed the glargine study, but two subjects on NPH and three on detemir interrupted the study because of plasma glucose >150 mg/dL. CONCLUSIONS: Compared with NPH and detemir, glargine provided greater metabolic activity and superior glucose control for up to 32 h.