Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects

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Erik Näslund, N King, S Mansten, N Adner, Jens Juul Holst, M Gutniak, P M Hellström

Recombinant glucagon-like peptide-1 (7-36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1 was given for 5 d by prandial subcutaneous injections (PSI) (76 nmol 30 min before meals, four times daily; a total of 302.4 nmol/24 h) or by continuous subcutaneous infusion (CSI) (12.7 nmol/h; a total of 304.8 nmol/24 h). This was performed in nineteen healthy obese subjects (mean age 44.2 (sem 2.5) years; BMI 39.0 (sem 1.2) kg/m(2)) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15 % reduction in mean food intake per meal (P=0.02) after 5 d treatment. A weight loss of 0.55 (sem 0.2) kg (P<0.05) was registered after 5 d with PSI of rGLP-1. Gastric emptying rate was reduced during both PSI (P<0.001) and CSI (P<0.05) treatment, but more rapidly and to a greater extent with PSI of rGLP-1. To conclude, a 5 d treatment of rGLP-1 at high doses by PSI, but not CSI, promptly slowed gastric emptying as a probable mechanism of action of increased satiety, decreased hunger and, hence, reduced food intake with an ensuing weight loss.

Original languageEnglish
JournalThe British Journal of Nutrition
Issue number3
Pages (from-to)439-46
Number of pages8
Publication statusPublished - Mar 2004

    Research areas

  • Adult, Cross-Over Studies, Double-Blind Method, Eating, Feeding Behavior, Female, Gastric Emptying, Glucagon, Glucagon-Like Peptide 1, Humans, Hunger, Infusions, Parenteral, Injections, Subcutaneous, Male, Middle Aged, Nausea, Obesity, Peptide Fragments, Protein Precursors, Recombinant Proteins, Satiation, Thirst, Weight Loss

ID: 132054581