High FODMAP Diet with Metformin in PreDM

The Impact of High or Low FODMAP Diets on Postprandial Glucose Response and Gut Microbiota in Individuals with Prediabetes Treated with Metformin: a Randomized Crossover Controlled-Feeding Trial

This is a prospective, double blinded, randomised cross over feeding trial examine high or low FODMAP diet in combination with metformin on postprandial glucose responses and gastrointestinal tolerability and gut microbiota profiles.

The trial will compare high or low FODMAP diet, each of 10 days duration in combination with 5 days metformin, separated by a washout period of at least 2 weeks.

Study Overview

• Status: Completed
• Conditions: PreDiabetes; Impaired Glucose Tolerance
• Intervention / Treatment: Combination product: High FODMAP diet with metformin; Combination product: Low FODMAP diet with metformin

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Sha Tin, Hong Kong
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-70 years
2. Body mass index 18 to 40 kg/m 2
3. Prediabetes defined as impaired fasting PG 5.6-6.9 mmol/l and/or impaired glucose tolerance with 2-hour PG 7.8-11.1 mmol/l on 75g oral glucose tolerance test (OGTT) and/or HbA1c 5.7-6.4% at screening

Exclusion Criteria:

1. Currently pregnant, lactating, as demonstrated by a positive pregnancy test at screening or planning pregnancy
2. Known current diabetes
3. Current or previous use of glucose-lowering or weight loss drugs in 3 months prior to screening
4. Concurrent participation in other weight loss or lifestyle intervention programmes
5. Current use or recent exposure to any medication that in the opinion of the investigator could have an influence on the patient's ability to participate in this study or on the performance of the test device.
6. Recent intake of prebiotic/probiotic or antibiotic, immunosuppressants (within 8 weeks of randomisation)
7. Extensive skin changes/diseases that preclude wearing the FGM on normal skin at the proposed application sites (e.g., extensive psoriasis, recent burns or severe sunburn, extensive eczema, extensive scarring, extensive tattoos, dermatitis herpetiformis).
8. Known uncontrolled thyrotoxicosis
9. Known vitamin B deficiency
10. Known irritable bowel syndrome or gastrointestinal disorders
11. Estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2 at screening
12. Current use of steroids
13. Have a known allergy to medical-grade adhesives
14. Known current or recent alcohol or drug abuse
15. Hypersensitivity to metformin
16. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma within 3 months of randomisation
17. Currently participating in another investigational study protocol where the testing or results may interfere with study compliance, diagnostic results, or data collection.
18. An identified protected vulnerable patient (including but not limited to those in detention, or a prisoner).
19. Participants who are on a vegetarian or vegan diet as their habitual diet at screening.
20. Participants with clinically significant food allergy to components of the study diet

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High FODMAP	Combination product: High FODMAP diet with metformin; Controlled High FODMAP diet (15g/day) from day 1-10, metformin XR 1000mg daily day 6-10 for each treatment period
Placebo Comparator: LOW FODMAP	Combination product: Low FODMAP diet with metformin; Controlled low FODMAP diet (3g/day) from day 1-10, metformin XR 1000mg daily day 6-10 for each treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in postprandial glycemia	incremental area under curve on continuous glucose monitoring post meal	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose response to 75g oral glucose tolerance test	fasting and postchallenge plasma glucose	10 days
Insulin response to 75g oral glucose tolerance test	insulin levels	10 days
Change in alpha diversity of gut microbiota	Changes in alpha diversity in gut microbiota	10 days
Change in beta diversity of gut microbiota	Changes in beta diversity in gut microbiota	10 days
Body weight	Differences in body weight between arms	10 days
Gastrointestinal symptoms	Measured on visual analogue scale 1-10 for each item, higher score indicates worse symptoms	10 days

Collaborators and Investigators

• Sponsor: Elaine Chow
• Collaborators: Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Actual): August 25, 2023
• Study Completion (Actual): October 15, 2023

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: November 16, 2022
• First Posted (Actual): November 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 2, 2025
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance; Physiological Effects of Drugs; Hypoglycemic Agents; Metformin
• Other Study ID Numbers: FODMAPMet

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No