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Randomised comparison of intravenous and subcutaneous routes of glucagon-like peptide-1 administration for lowering plasma glucose in hyperglycaemic subjects with type 2 diabetes.
Quast, Daniel R; Lancaster, Dara; Xie, Cong; Bound, Michelle J; Grivell, Jacqueline; Jones, Karen L; Horowitz, Michael; Meier, Juris J; Wu, Tongzhi; Rayner, Christopher K; Nauck, Michael A.
Afiliación
  • Quast DR; Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
  • Lancaster D; Diabetes, Endocrinology and Metabolism Section, Department of Internal Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
  • Xie C; Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
  • Bound MJ; Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
  • Grivell J; Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
  • Jones KL; Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
  • Horowitz M; Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
  • Meier JJ; Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
  • Wu T; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.
  • Rayner CK; Department of Internal Medicine, Augusta-Hospital, Bochum, Germany.
  • Nauck MA; Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
Diabetes Obes Metab ; 26(9): 3897-3905, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38951936
ABSTRACT

AIM:

To perform a direct, double-blind, randomised, crossover comparison of subcutaneous and intravenous glucagon-like peptide-1 (GLP-1) in hyperglycaemic subjects with type 2 diabetes naïve to GLP-1-based therapy. MATERIALS AND

METHODS:

Ten fasted, hyperglycaemic subjects (1 female, age 63 ± 10 years [mean ± SD], glycated haemoglobin 73.5 ± 22.0 mmol/mol [8.9% ± 2.0%], both mean ± SD) received subcutaneous GLP-1 and intravenous saline, or intravenous GLP-1 and subcutaneous saline. Infusion rates were doubled every 120 min (1.2, 2.4, 4.8 and 9.6 pmol·kg-1·min-1 for subcutaneous, and 0.3, 0.6, 1.2 and 2.4 pmol·kg-1·min-1 for intravenous). Plasma glucose, total and intact GLP-1, insulin, C-peptide, glucagon and gastrointestinal symptoms were evaluated over 8 h. The results are presented as mean ± SEM.

RESULTS:

Plasma glucose decreased more with intravenous (by ~8.0 mmol/L [144 mg/dL]) than subcutaneous GLP-1 (by ~5.6 mmol/L [100 mg/dL]; p < 0.001). Plasma GLP-1 increased dose-dependently, but more with intravenous than subcutaneous for both total (∆max 154.2 ± 3.9 pmol/L vs. 85.1 ± 3.8 pmol/L; p < 0.001), and intact GLP-1 (∆max 44.2 ± 2.2 pmol/L vs. 12.8 ± 2.2 pmol/L; p < 0.001). Total and intact GLP-1 clearance was higher for subcutaneous than intravenous GLP-1 (p < 0.001 and p = 0.002, respectively). The increase in insulin secretion was greater, and glucagon was suppressed more with intravenous GLP-1 (p < 0.05 each). Gastrointestinal symptoms did not differ (p > 0.05 each).

CONCLUSIONS:

Subcutaneous GLP-1 administration is much less efficient than intravenous GLP-1 in lowering fasting plasma glucose, with less stimulation of insulin and suppression of glucagon, and much less bioavailability, even at fourfold higher infusion rates.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glucemia / Estudios Cruzados / Diabetes Mellitus Tipo 2 / Péptido 1 Similar al Glucagón / Hiperglucemia / Hipoglucemiantes Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Diabetes Obes Metab Asunto de la revista: ENDOCRINOLOGIA / METABOLISMO Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glucemia / Estudios Cruzados / Diabetes Mellitus Tipo 2 / Péptido 1 Similar al Glucagón / Hiperglucemia / Hipoglucemiantes Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Diabetes Obes Metab Asunto de la revista: ENDOCRINOLOGIA / METABOLISMO Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido