Comparison of the dose-response pharmacodynamic profiles of detemir and glargine in severely obese patients with type 2 diabetes: A single-blind, randomised cross-over trial.

Autor: Bilz S; Division of Endocrinology and Diabetes, Kantonsspital St. Gallen, St. Gallen, Switzerland., Flückiger M; Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland., Meienberg F; Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland., Falconnier C; Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland., Keller U; Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland., Puder JJ; Division of Endocrinology, Diabetes and Metabolism, University Hospital Lausanne, Lausanne, Switzerland.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Aug 16; Vol. 13 (8), pp. e0202007. Date of Electronic Publication: 2018 Aug 16 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0202007
Abstrakt: Background: Despite their widespread use in this population, data on the pharmacodynamic (PD) properties of the insulin analogs detemir and glargine in severely obese patients with type 2 diabetes are lacking.
Methods: The primary objective of the study was to compare the PD properties of two different doses of the basal insulin analogs detemir and glargine in patients with type 2 diabetes and a BMI > 35 kg/m2. PD data were derived from euglycemic clamp studies over 30 hours and each subject was studied for four times after the subcutaneous injection of a lower (0.8 U/kg body weight) and higher (1.6 U/kg body weight) dose of both detemir and glargine using a single-blind, randomised cross-over design.
Results: Six male and four female patients with type 2 diabetes and a mean BMI of 43.2±5.1 kg/m2 (mean age 55.7±2 years, mean HbA1c 7.2±0.3%) completed the study. The total GIRAUC0-30 (mean difference 1224 mg/kg, 95%CI 810-1637, p = 0.00001), GIRAUC0-24 (mean difference 1040 mg/kg, 95%CI 657-1423; p = 0.00001), GIRAUC24-30 (mean difference 181 mg/kg, 95%CI 64-298; p = 0.004), GIRmax (mean difference 0.93 mg/kg/min, 95%CI 0.22-1.64, p = 0.01) and time to GIRmax (+1.9 hours, 95%CI 0.5-3.2; p = 0.009) were higher after the higher doses of both insulins, without significant differences between detemir and glargine. However, during the last 6 hours of the clamp the GIRAUC24-30 was significantly increased with glargine (mean difference 122 mg/kg, 95%CI 6-237, p = 0.043), reflecting a more pronounced late glucose lowering effect.
Conclusions: A clear dose-response relationship can be demonstrated for both insulin analogs, even at very high doses in severely obese patients with type 2 diabetes. Compared to detemir, glargine has a more pronounced late glucose lowering effect 24-30 h after its injection.
Trial Registration: Controlled-Trials.com ISRCTN57547229.
Competing Interests: The study was an investigator driven study supported by an unrestricted educational grant from Novo Nordisk Pharma Switzerland AG. U. K. has received consulting fees from NovoNordisk and Sanofi-Aventis. J. P. has received consulting fees and fees for speaking at meetings from NovoNordisk and consulting fees from Sanof-Aventis. S.B. has received fees for speaking at meetings from NovoNordisk and Sanofi-Aventis. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
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