The Metabolic Effects of Oral Tributyrin Administration (TRIMET)

The Metabolic Effects of Oral Tributyrin Administration in Overweight/Obese Individuals

The goal of this double-blinded randomized clinical cross-over trial is to investigate the metabolic and appetite regulating effects of oral tributyrin (a butyrate pro-drug) administration vs placebo.

The main questions it aims to answer are:

• Does tributyrin have glucose lowering properties in humans?
• Does tributyrin reduce appetite in humans?

A sample size calculation estimated a minimum of 10 participants. We expect to include 12 participants in this study. Tributyrin or placebo is ingested once or twice daily for 2x2 weeks, separated by a washout period of minimum 2 weeks. On trial day following each 2-week period we assess:

• Postprandial blood sugar levels
• Hunger sensations (questionnaire)
• Enteroendocrine hormone secretion (GLP-1, GIP, PYY, LEAP2, ghrelin)
• Cardiac function (echocardiography) - An exploratory study evaluating the hemodynamic effects assessed by echocardiography is anticipated to be published separately.
• Caloric intake (ad libitum meal test)
• Gastric emptying rate (acetaminophen test)
• Resting metabolic rate (indirect calorimetry).

While at home, subjects will wear a sleep monitoring device for three consecutive nights and deliver fecal samples for analysis of short-chain fatty acid content and microbiota composition.

Study Overview

• Status: Recruiting
• Conditions: Healthy Overweight/Obese
• Intervention / Treatment: Dietary supplement: tributyrin; Dietary supplement: Control

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Simon M Denning, MD; Phone Number: 0045 78450000; Email: simon.denning@clin.au.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • SDCA / Medical Research Laboratory
    • Contact: Simon M Denning, MD; Phone Number: 004578450000; Email: simon.denning@clin.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A body mass index (BMI) between 30-45 kg/m2
• Older than 18 years of age
• HbA1c < 48 mmol/mol
• Hemoglobin within normal range (females: 7.3-9.5 mmol/L, males: 8.3-10.5 mmol/L)
• Written and oral consent to participate

Exclusion Criteria:

• Medications affecting glucose metabolism and/or appetite (e.g. insulin, metformin, GLP-1 analogues)
• Special diet (HCLF, ketogenic diets, vegan/vegetarian)
• Ongoing cancer or other acute/chronic serious diseases (determined by PI)
• Inability to understand Danish or English
• Abnormal blood samples at screening visit (determined by PI and co-investigators)
• Deemed unsuitable to participate by the PI and co-investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral tributyrin; Oral ingestion of tributyrin	Dietary supplement: tributyrin; Oral ingestion of tributyrin (liquid) once daily (20 g x 1) for 7 days, then twice daily (20 g x 2) for 7 days.
Placebo Comparator: Control; Oral ingestion of placebo	Dietary supplement: Control; Oral ingestion of water (liquid) with added bitter substance once daily (20 ml x 1) for 7 days, then twice daily (20 ml x 2) for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial glucose	iAUC of plasma glucose after ingestion of mixed meal	During trial day, time 120-300 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Butyrate	Plasma concentrations of butyrate	During trial day, time 0-300 minutes
Caloric intake	Caloric intake (kcal) during ad libitum meal test	Time 300 minutes
Gastric emptying assessed by acetaminophen	Plasma concentration of acetaminophen following oral acetaminophen intake	From ingestion of mixed meal test with acetaminophen, time 120-240 minutes
GLP-1	Plasma concentrations of GLP-1	During trial day, time 0-300 minutes
GIP	Plasma concentrations of GIP	During trial day, time 0-300 minutes
LEAP2	Plasma concentrations of LEAP2	During trial day, time 0-300 minutes
PYY	Plasma concentrations of PYY	During trial day, time 0-300 minutes
Ghrelin	Plasma concentrations of ghrelin	During trial day, time 0-300 minutes
Insulin	Plasma concentrations of insulin	During trial day, time 0-300 minutes
C-peptide	Plasma concentrations of c-peptide	During trial day, time 0-300 minutes
Glucagon	Plasma concentrations of glucagon	During trial day, time 0-300 minutes
Cardiac function	Echocardiographic assessment of cardiac output, left ventricular ejection fraction, global longitudinal strain, tricuspid annular plane systolic excursion (TAPSE), systemic vascular resistance	Time 0 and 90 minutes
β-hydroxybutyrate	Plasma concentrations of β-hydroxybutyrate	During trial day, time 0-300 minutes
Lactate	Plasma concentrations of lactate	During trial day, time 0-300 minutes
C-reactive protein (CRP)	Plasma concentrations of CRP	On trial day, time 0 minutes
Tumor Necrosis Factor ⍺ (TNF-⍺)	Plasma concentrations of TNF-⍺	On trial day, time 0 minutes
Interleukin 6 (IL-6)	Plasma concentrations of IL-6	On trial day, time 0 minutes
Interleukin 10 (IL-10)	Plasma concentrations of IL-10	On trial day, time 0 minutes
Lipopolysaccharide Binding Protein (LPB)	Plasma concentrations of LPB	On trial day, time 0 minutes
Cortisol	Plasma concentration of cortisol	On trial day, time 0 minutes
Triglyceride	Plasma concentrations of triglyceride	During trial day, time 0-300 minutes
FFA	Plasma concentrations of free fatty acids	During trial day, time 0-300 minutes
Energy expenditure	Indirect calorimetry	After 60 and 150 minutes approximately
Sleep	Assessment of sleep duration and stages	Three nights at the end of the 2 week period at home
Fecal butyrate	Fecal concentrations of butyrate	Day 0, 7, 14 during the 2 week period
Microbiome composition	Analysis of microbiome composition and metagenomics performed on fecal samples	Day 0, 7, 14 during the 2 week period
Subjective appetite - appetite questionaire	We will assess subjective appetite sensations with a recommended primary scale for self-reported appetite in healthy adults. The scale includes five questions addressing hunger, fullness, satiety, desire to eat and prospective consumption. The participants answer on a computer or tablet by sliding a button on a horizontal line (Visual Analog Scale) with left being eg. "Not hungry at all" to right "As hungry as I have ever felt".	0, 60, 120, 180, 240, 300 minutes

Collaborators and Investigators

• Sponsor: University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 11, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Appetite; Butyrate; Glucose metabolism; Tributyrin
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; tributyrin
• Other Study ID Numbers: 1-10-72-110-25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The corresponding author will make data available on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No