Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects.
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.
Division of Surgery, Karolinska Institutet-Danderyd Hospital, SE-182 88 Danderyd, Sweden. Erik.Naslund@kir.ds.sll.se
Erik
E
Näslund
N
N
King
S
S
Mansten
N
N
Adner
J J
JJ
Holst
M
M
Gutniak
P M
PM
Hellström
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D006815:Hunger / Q000187:drug effects; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011498:Protein Precursors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012527:Satiation / Q000187:drug effects; D013894:Thirst / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects*
D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; D052216:Glucagon-Like Peptide 1; D005934:Glucagon