Open AccessComparison 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
Author(s) -
Stefan Bilz,
Miriam Flückiger,
Fabian Meienberg,
Claudine Falconnier,
Ulrich Keller,
Jardena J. Puder
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0202007
Subject(s) - medicine , pharmacodynamics , type 2 diabetes , insulin detemir , insulin glargine , diabetes mellitus , population , gastroenterology , basal (medicine) , endocrinology , pharmacokinetics , environmental health
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/m 2 . 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/m 2 (mean age 55.7±2 years, mean HbA1c 7.2±0.3%) completed the study. The total GIR AUC0-30 (mean difference 1224 mg/kg, 95%CI 810–1637, p = 0.00001), GIR AUC0-24 (mean difference 1040 mg/kg, 95%CI 657–1423; p = 0.00001), GIR AUC24-30 (mean difference 181 mg/kg, 95%CI 64–298; p = 0.004), GIR max (mean difference 0.93 mg/kg/min, 95%CI 0.22–1.64, p = 0.01) and time to GIR max (+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 GIR AUC24-30 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 .