TY - JOUR

T1 - The effect of a subcutaneous infusion of GLP-1, OXM and PYY on Energy intake and Expenditure in Obese volunteers

AU - Tan, Tricia

AU - Behary, Preeshila

AU - Tharakan, George

AU - Minnion, James

AU - Al-Najim, Werd

AU - Wewer Albrechtsen, Nicolai J

AU - Holst, Jens J

AU - Bloom, Stephen R

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Background: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment for 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 post-prandially after RYGB, which has been postulated to contribute to its metabolic benefits.Objective: We hypothesised that infusion of the three gut hormones to achieve levels similar to those encountered post-prandially 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 randomised to receive an infusion of GOP or placebo in a single-blinded randomised placebo-controlled cross-over 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 measured using a ventilated hood calorimeter.Results: Post-prandial 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 the first time that an acute continuous subcutaneous infusion of GOP, replicating the post-prandial 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.

AB - Background: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment for 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 post-prandially after RYGB, which has been postulated to contribute to its metabolic benefits.Objective: We hypothesised that infusion of the three gut hormones to achieve levels similar to those encountered post-prandially 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 randomised to receive an infusion of GOP or placebo in a single-blinded randomised placebo-controlled cross-over 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 measured using a ventilated hood calorimeter.Results: Post-prandial 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 the first time that an acute continuous subcutaneous infusion of GOP, replicating the post-prandial 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.

KW - Journal Article

U2 - 10.1210/jc.2017-00469

DO - 10.1210/jc.2017-00469

M3 - Journal article

C2 - 28379519

VL - 102

SP - 2364

EP - 2372

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -