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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.
Bilz, Stefan; Flückiger, Miriam; Meienberg, Fabian; Falconnier, Claudine; Keller, Ulrich; Puder, Jardena J.
Afiliación
  • 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.
PLoS One ; 13(8): e0202007, 2018.
Article en En | MEDLINE | ID: mdl-30114246
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Insulina Detemir / Insulina Glargina / Obesidad Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Insulina Detemir / Insulina Glargina / Obesidad Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos