The Effect of a Subcutaneous Infusion of GLP-1, OXM, and PYY on Energy Intake and Expenditure in Obese Volunteers

• Published in: The journal of clinical endocrinology and metabolism Vol. 102; no. 7; pp. 2364 - 2372
• Main Authors: Tan, Tricia, Behary, Preeshila, Tharakan, George, Minnion, James, Al-Najim, Werd, Albrechtsen, Nicolai J. Wewer, Holst, Jens J., Bloom, Stephen R.
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.07.2017; Oxford University Press
• Subjects: Adult; Analysis of Variance; Appetite; Area Under Curve; Body Mass Index; Clinical s; Cross-Over Studies; Energy expenditure; Energy intake; Energy measurement; Energy Metabolism - drug effects; Female; Follow-Up Studies; Food; Food intake; Gastric bypass; Gastric Bypass - methods; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - administration & dosage; Hormones; Humans; Infusions, Subcutaneous; Male; Middle Aged; Obesity; Obesity, Morbid - surgery; Oxyntomodulin - administration & dosage; Pain Measurement; Patient Safety; Peptide YY - administration & dosage; Randomization; Replication; Risk Assessment; Single-Blind Method; Surgery; Treatment Outcome; United Kingdom; Volunteers
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2017-00469

Abstract Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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. A combined subcutaneous infusion of GLP-1, OXM, and PYY given to obese volunteers, matching the postprandial levels of the hormones as observed post RYGB, led to a 32% reduction in total food intake.