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
Volume91
Issue number3
Pages (from-to)439-46
Number of pages8
ISSN0007-1145
DOIs
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