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

TY - JOUR

T1 - Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects

AU - Näslund, Erik

AU - King, N

AU - Mansten, S

AU - Adner, N

AU - Holst, Jens Juul

AU - Gutniak, M

AU - Hellström, P M

PY - 2004/3

Y1 - 2004/3

N2 - 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.

AB - 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.

KW - Adult

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Eating

KW - Feeding Behavior

KW - Female

KW - Gastric Emptying

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Hunger

KW - Infusions, Parenteral

KW - Injections, Subcutaneous

KW - Male

KW - Middle Aged

KW - Nausea

KW - Obesity

KW - Peptide Fragments

KW - Protein Precursors

KW - Recombinant Proteins

KW - Satiation

KW - Thirst

KW - Weight Loss

U2 - 10.1079/BJN20031064

DO - 10.1079/BJN20031064

M3 - Journal article

C2 - 15005830

SN - 0007-1145

VL - 91

SP - 439

EP - 446

JO - British Journal of Nutrition

JF - British Journal of Nutrition

IS - 3

ER -