O106 Maximising the benefits of bariatric surgery through targeting ghrelin: a randomised, double-blind, placebo-controlled crossover study in people with suboptimal weight loss after bariatric surgery

• DOI: 10.1093/bjs/znac242.106
• Publication Date: 2022-11-01T17:58:10Z
• Authors: R Zakeri; A Carnemolla; P Marvasti; J Mok; F Jassil; K Chaiyasoot; J Lichfield; M Alves; R Mansoor; R Omar; R Batterham
• Keywords: Orexigenic; Sleeve gastrectomy

Abstract Introduction One in 5 people have a suboptimal weight-loss (WL) response to bariatric surgery. The causes are unclear, but patients report resumed hunger and increased food intake, eating behaviours driven by the orexigenic hormone, ghrelin. This proof-of-concept study aimed evaluate impact of reducing circulating acyl-ghrelin, biologically active isoform, on appetite energy intake with WL aberrant ghrelin profile after Methods Thirty-five <20%WL from 12 months Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) underwent 10 days treatment novel, highly-selective o-acyltransferase inhibitor, GLWL-01, placebo. primary endpoint was within-person change ad libitum during test meal day 10. Secondary endpoints assessed subjective appetite, cravings, macronutrient gut hormones, cardiometabolic body composition. Ethical approval obtained. Results Thirty-one participants (26 RYGB, 9 SG) completed both cycles. GLWL-01 produced 58.9±27.2% decrease fasting plasma acyl-ghrelin 29.3±27.1% increase desacyl-ghrelin days. Marked reduction hunger, cravings hedonic influence observed however objective measures – free-living did not change. Circulating levels cardiovascular risk-conferring lipoproteins significantly improved no adverse glycaemic control observed. Conclusion Pharmacological modulation system may be used as part personalised therapeutic approach optimise clinical outcomes Take-home message first-in-human mechanistic shows that pharmacological is promising strategy for maximising weight loss