British Journal of Nutrition

Research Article

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

Erik Näslunda1 c1, N. Kinga2, S. Manstena3, N. Adnera3, J. J. Holsta4, M. Gutniaka3 and P. M. Hellströma5

a1 Division of Surgery, Karolinska Institutet Danderyd Hospital, SE-182 88 Danderyd, Sweden

a2 Department of Biopsychology, University of Leeds, Leeds, UK

a3 Division of Medicine, Karolinska Institutet South Hospital, Stockholm, Sweden

a4 Department of Medical Physiology, University of Copenhagen, Copenhagen, Denmark

a5 Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

Abstract

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.

(Received June 21 2003)

(Revised October 14 2003)

(Accepted November 06 2003)

Correspondence:

c1 *Corresponding author: Dr Erik Näslund, fax +46 8 655 77 66, email Erik.Naslund@kir.ds.sll.se

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