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

OBJECTIVETo compare the pharmacokinetics and pharmacodynamics of NPH, glargine, and detemir insulins in type 2 diabetic subjects.RESEARCH DESIGN AND METHODSThis 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.RESULTSThe 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.CONCLUSIONSCompared with NPH and detemir, glargine provided greater metabolic activity and superior glucose control for up to 32 h.

Iowa medicaid 2: lapse of glycemic control on abrupt transition from insulin glargine to insulin detemir in type 2 diabetes mellitus

“…This finding is consistent with observations in another study in which a substantial reduction in daily dose of insulin glargine was noted with a transition from insulin detemir in subjects with type 2 Diabetes [9]. Several other studies have also documented a requirement of a higher daily dose of insulin detemir in comparison to insulin glargine to attain comparable glycemic control [10][11][12][13][14][15][16][17][18][19]. Thus, a higher daily dose and twice daily administration of insulin detemir may have been required to achieve desirable glycemic goal in this study as documented in previous studies in most subjects with both Type 1 and Type 2 diabetes [1,[10][11][12][13][14][15][16][17][18][19].…”

“…Several other studies have also documented a requirement of a higher daily dose of insulin detemir in comparison to insulin glargine to attain comparable glycemic control [10][11][12][13][14][15][16][17][18][19]. Thus, a higher daily dose and twice daily administration of insulin detemir may have been required to achieve desirable glycemic goal in this study as documented in previous studies in most subjects with both Type 1 and Type 2 diabetes [1,[10][11][12][13][14][15][16][17][18][19]. The requirement for a higher daily dose for insulin detemir in comparison to insulin glargine in order to achieve identical glycemic control in type 2 Diabetes is further confirmed in a recent study examining pharmacokinetics and pharmacodynamics of these insulins [20].…”

Pharmacokinetics and Pharmacodynamics of Insulin Glargine Given in the Evening as Compared With in the Morning in Type 2 Diabetes

“…At 2120 min, a primed sterile, pyrogen-free constant infusion (0.222 mmol/kg/min) of [6,6-2 H 2 ]-glucose (Cambridge Isotope Laboratories, Cambridge, MA) was started and maintained throughout the experiment to determine glucose kinetics. A variable rate of a 20% dextrose solution enriched to 4% with [6,6-2 H 2 ]-glucose was used to clamp the PG concentration at the desired target of 100 mg/dL for 24 h (14) and to avoid non-steady-state errors in the measurement of glucose turnover, as described previously (22). At 1000 or 2200 h, a subcutaneous injection of 0.4 units/kg insulin glargine (Lantus 100 units/mL) was administered by means of injection with a 0.5-mL insulin syringe into the abdominal area.…”

“…The plasma free insulin concentration was measured by radioimmunoassay after polyethylene glycol extraction of antibodies from the plasma (23). Plasma free fatty acid (FFA), glycerol, b-OHbutyrate, C-peptide, and glucagon concentrations were measured by previously described methods (14). Glucose enrichment was determined on its penta-acetate (penta-O-acetylb-D-glucopyranose) derivative by gas chromatography-mass spectrometry (HP 6890 II GC, HP 5973A GC/MS; Hewlett-Packard, Palo Alto, CA) in electron impact ionization mode monitoring the ions 200 and 202 for the unlabeled and [6,6-2 H 2 ]-glucose, respectively (24).…”

“…Yet, an indirect comparison of PK and PD between studies, where glargine was given in the evening (14) compared with the morning (15)(16)(17), suggests important differences in action profiles, although in such a comparison the contribution of circadian changes in insulin sensitivity should be taken into account (18,19).…”