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.

Details

Serval ID
serval:BIB_158F4A0E8596
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
PloS one
Author(s)
Bilz S., Flückiger M., Meienberg F., Falconnier C., Keller U., Puder J.J.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
13
Number
8
Pages
e0202007
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
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.
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.
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.
Controlled-Trials.com ISRCTN57547229.
Keywords
Adult, Biomarkers, Blood Glucose/drug effects, C-Peptide, Cross-Over Studies, Diabetes Mellitus, Type 2/complications, Diabetes Mellitus, Type 2/drug therapy, Dose-Response Relationship, Drug, Female, Glucose Clamp Technique, Humans, Insulin Detemir/administration & dosage, Insulin Detemir/pharmacokinetics, Insulin Glargine/administration & dosage, Insulin Glargine/pharmacokinetics, Male, Middle Aged, Obesity/complications
Pubmed
Web of science
Open Access
Yes
Create date
31/08/2018 11:15
Last modification date
20/08/2019 12:44
Usage data