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

Published online by Cambridge University Press:  09 March 2007

Erik Näslund ,
N. King ,
S. Mansten ,
N. Adner ,
J. J. Holst ,
M. Gutniak  and
P. M. Hellström
Erik Näslund*
Affiliation:
Division of Surgery, Karolinska Institutet Danderyd Hospital, SE-182 88 Danderyd, Sweden
N. King
Affiliation:
Department of Biopsychology, University of Leeds, Leeds, UK
S. Mansten
Affiliation:
Division of Medicine, Karolinska Institutet South Hospital, Stockholm, Sweden
N. Adner
Affiliation:
Division of Medicine, Karolinska Institutet South Hospital, Stockholm, Sweden
J. J. Holst
Affiliation:
Department of Medical Physiology, University of Copenhagen, Copenhagen, Denmark
M. Gutniak
Affiliation:
Division of Medicine, Karolinska Institutet South Hospital, Stockholm, Sweden
P. M. Hellström
Affiliation:
Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden
*
*Corresponding author: Dr Erik Näslund, fax +46 8 655 77 66, email Erik.Naslund@kir.ds.sll.se
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Abstract

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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 5d by prandial subcutaneous injections (PSI) (76nmol 30min before meals, four times daily; a total of 302·4nmol/24h) or by continuous subcutaneous infusion (CSI) (12·7nmol/h; a total of 304·8nmol/24h). This was performed in nineteen healthy obese subjects (mean age 44·2 (sem 2·5) years; BMI 39·0 (sem 1·2)kg/m2) 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 5d treatment. A weight loss of 0·55 (sem 0·2) kg (P<0·05) was registered after 5d 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 5d 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.

Keywords

Glucagon-like peptide-1ObesityGastric emptyingWeight loss
Type
Research Article
Information
British Journal of Nutrition , Volume 91 , Issue 3 , March 2004 , pp. 439 - 446
Copyright
Copyright © The Nutrition Society 2004

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