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.