Volume 91, Issue 3, March (2004), pp. 439-446 © The Author 2004
doi:10.1079/BJN20031064

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

Erik Näslund¹, N. King², S. Mansten³, N. Adner³, J. J. Holst⁴, M. Gutniak³, P. M. Hellström^5
1Division of Surgery, Karolinska Institutet Danderyd Hospital, SE-182 88 , Danderyd, Sweden
²Department of Biopsychology, University of Leeds, Leeds, UK
³Division of Medicine, Karolinska Institutet South Hospital, Stockholm, Sweden
⁴Department of Medical Physiology, University of Copenhagen, Copenhagen, Denmark
⁵Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden

 (Received 21 June 2003–Revised 14 October 2003–Accepted 6 November 2003)

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/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 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.

Keywords:
Glucagon-like peptide-1 Obesity Gastric emptying Weight loss

Abbreviations:
CSI, continuous subcutaneous infusion, GLP-1, glucagon-like peptide-1, ITT, intention to treat, PSI, prandial subcutaneous injections, rGLP-1, recombinant glucagon-like peptide-1, SC, subcutaneous, T50, gastric half-emptying time, VAS, visual analogue scale, VIKTORIA, universal eating monitor