title: Coinfusion of low-dose GLP-1 and glucagon in man results in a reduction in food intake.
abstract: Obesity is a growing epidemic, and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs that aim to cause effective weight loss with minimal side effects. Both glucagon and GLP-1 reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. We hypothesized that the combination of both peptides, administered at doses that are individually subanorectic, would reduce appetite, while GLP-1 would protect against the hyperglycemic effect of glucagon. In this double-blind crossover study, subanorectic doses of each peptide alone, both peptides in combination, or placebo was infused into 13 human volunteers for 120 min. An ad libitum meal was provided after 90 min, and calorie intake determined. Resting energy expenditure was measured by indirect calorimetry at baseline and during infusion. Glucagon or GLP-1, given individually at subanorectic doses, did not significantly reduce food intake. Coinfusion at the same doses led to a significant reduction in food intake of 13%. Furthermore, the addition of GLP-1 protected against glucagon-induced hyperglycemia, and an increase in energy expenditure of 53 kcal/day was seen on coinfusion. These observations support the concept of GLP-1 and glucagon dual agonism as a possible treatment for obesity and diabetes.
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Jaimini
authors.initials: J
authors.lastname: Cegla
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Troke
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Ben
authors.initials: B
authors.lastname: Jones
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: George
authors.initials: G
authors.lastname: Tharakan
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Julia
authors.initials: J
authors.lastname: Kenkre
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McCullough
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Chung Thong
authors.initials: CT
authors.lastname: Lim
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Nassim
authors.initials: N
authors.lastname: Parvizi
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hussein
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Chambers
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: James
authors.initials: J
authors.lastname: Minnion
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Joyceline
authors.initials: J
authors.lastname: Cuenco
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Karim
authors.initials: K
authors.lastname: Meeran
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Tricia M
authors.initials: TM
authors.lastname: Tan
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K. s.bloom@imperial.ac.uk.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004435:Eating / Q000187:drug effects*; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D055815:Young Adult
chemical_list: D052216:Glucagon-Like Peptide 1; D005934:Glucagon