title: The Effect of a Subcutaneous Infusion of GLP-1, OXM, and PYY on Energy Intake and Expenditure in Obese Volunteers.
abstract: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits.
  
  
  
  We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers.
  
  
  
  Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter.
  
  
  
  Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed.
  
  
  
  This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity.
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Hammersmith Hospital, Imperial College London, London W12 0HS, United Kingdom.
authors.forename: Tricia
authors.initials: T
authors.lastname: Tan
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Hammersmith Hospital, Imperial College London, London W12 0HS, United Kingdom.
authors.forename: Preeshila
authors.initials: P
authors.lastname: Behary
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Hammersmith Hospital, Imperial College London, London W12 0HS, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Tharakan
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Hammersmith Hospital, Imperial College London, London W12 0HS, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Minnion
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Hammersmith Hospital, Imperial College London, London W12 0HS, United Kingdom.
authors.forename: Werd
authors.initials: W
authors.lastname: Al-Najim
authors.affiliation: Department of Biochemical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Nicolai J Wewer
authors.initials: NJW
authors.lastname: Albrechtsen
authors.affiliation: Department of Biochemical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Hammersmith Hospital, Imperial College London, London W12 0HS, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D015992:Body Mass Index; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D015390:Gastric Bypass / Q000379:methods*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D006801:Humans; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000601:surgery*; D053772:Oxyntomodulin / Q000008:administration & dosage*; D010147:Pain Measurement; D061214:Patient Safety; D019894:Peptide YY / Q000008:administration & dosage*; D018570:Risk Assessment; D016037:Single-Blind Method; D016896:Treatment Outcome; D006113:United Kingdom; D014838:Volunteers
chemical_list: D053772:Oxyntomodulin; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1