title: Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia.
abstract: Glucagon and glucagon-like peptide (GLP)-1 are the primary products of proglucagon processing from the pancreas and gut, respectively. Giving dual agonists with glucagon and GLP-1 activity to diabetic, obese mice causes enhanced weight loss and improves glucose tolerance by reduction of food intake and by increase in energy expenditure (EE). We aimed to observe the effect of a combination of glucagon and GLP-1 on resting EE and glycemia in healthy human volunteers. In a randomized, double-blinded crossover study, 10 overweight or obese volunteers without diabetes received placebo infusion, GLP-1 alone, glucagon alone, and GLP-1 plus glucagon simultaneously. Resting EE--measured using indirect calorimetry--was not affected by GLP-1 infusion but rose significantly with glucagon alone and to a similar degree with glucagon and GLP-1 together. Glucagon infusion was accompanied by a rise in plasma glucose levels, but addition of GLP-1 to glucagon rapidly reduced this excursion, due to a synergistic insulinotropic effect. The data indicate that drugs with glucagon and GLP-1 agonist activity may represent a useful treatment for type 2 diabetes and obesity. Long-term studies are required to demonstrate that this combination will reduce weight and improve glycemia in patients.
authors.affiliation: Section of Investigative Medicine, Imperial College London, London, U.K.
authors.forename: Tricia M
authors.initials: TM
authors.lastname: Tan
authors.forename: Benjamin C T
authors.initials: BC
authors.lastname: Field
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McCullough
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Troke
authors.forename: Edward S
authors.initials: ES
authors.lastname: Chambers
authors.forename: Victoria
authors.initials: V
authors.lastname: Salem
authors.forename: Juan
authors.initials: J
authors.lastname: Gonzalez Maffe
authors.forename: Kevin C R
authors.initials: KC
authors.lastname: Baynes
authors.forename: Akila
authors.initials: A
authors.lastname: De Silva
authors.forename: Alexander
authors.initials: A
authors.lastname: Viardot
authors.forename: Ali
authors.initials: A
authors.lastname: Alsafi
authors.forename: Gary S
authors.initials: GS
authors.lastname: Frost
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000328:Adult; D002153:Calorimetry, Indirect; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged
chemical_list: D052216:Glucagon-Like Peptide 1; D005934:Glucagon