Acute TRPTI™ (oleoylethanolamide) supplementation enhances incretin hormone responses: a fixed-sequence crossover study

Background: Oleoylethanolamide (OEA) is an endogenous lipid mediator involved in nutrient sensing and gut-derived hormonal signalling. TRPTI™ is a bioavailable OEA formulation designed to support metabolic and appetite-related pathways. This study evaluated the acute metabolic effects of TRPTI™ in healthy adults under controlled feeding conditions. Methods: In this fixed-sequence, single-blind, placebo-controlled, three-period crossover study, 37 adults (BMI 25-34.9 kg/m²) received a single dose of a placebo, 150 mg TRPTI™, or 300 mg TRPTI™ following an overnight fast. Blood samples were collected over 8 hours, with standardised meals provided at 15 minutes and 4 hours post dose. Time-course responses of GLP-1, GIP, DPP-4, insulin, glucose, and glucagon were analysed. Results: Baseline adjusted GLP-1 and GIP AUC analyses demonstrated significant treatment effects across multiple pre-specified meal-related periods. The 300 mg TRPTI™ dose produced the greatest incretin responses and was significantly greater than placebo during selected pre-specified post-dosing and post-prandial periods, with elevations detectable within 15 minutes of ingestion. At key timepoints, GLP-1 concentrations were significantly higher (approximately 20-25%) than placebo. Similar significant increases were observed for GIP. Significant concentration changes in circulating DPP-4 were observed at later time points, indicating a potential association between TRPTI™ supplementation and serum DPP-4 modulation. Both TRPTI™ doses showed acute tolerability with safety biomarkers remaining within normal ranges. A statistically significant reduction in meal consumption was observed in both TRPTI™ groups. Conclusions: A single 300 mg dose of TRPTI™ enhances post-meal GLP-1 and GIP responses and demonstrates rapid engagement of GLP-1, GIP and DPP-4, supporting further investigation of its role in nutritional strategies targeting metabolic health. Clinical trial registration: https://clinicaltrials.gov/study/NCT06840080, identifier NCT06840080.