Fiber and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance

Fiber Supplementation and Metformin Combination Therapy in Adolescents With Severe Obesity and Insulin Resistance: Interactions With the Gut Microbiome.

This is a 12-month, single center, three-arm parallel design, double-blind, randomized clinical trial, to compare the effects of supplemental dietary fiber and metformin (MET) alone and in combination over 12 months on glucose metabolism (insulin resistance [IR]), inflammation and BMI in adolescents with obesity and IR, and to assess the relationship between therapeutic intervention(s) and changes in gut microbiome composition and function.

Since MET and FIBER have been shown to reduce weight and increase insulin sensitivity through distinct but overlapping mechanisms of action, our central hypothesis is that the combination of FIBER + MET will have a synergistic effect and be more effective than FIBER or MET alone in improving metabolic function (IR) and reducing BMI and inflammation in adolescents with obesity, IR and family history (FM) of T2DM.

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Study Overview

• Status: Recruiting
• Conditions: Insulin Resistance; Obesity, Childhood
• Intervention / Treatment: Drug: Metformin 850 mg oral tablet bid; Dietary supplement: Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Andrea M Haqq, MD, MHS; Phone Number: 780-492-0015; Email: haqq@ualberta.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2E1
      • Recruiting
      • University of Alberta
      • Contact: Andrea M Haqq, MD, MHS; Phone Number: 780-492-0015; Email: haqq@ualberta.ca
      • Principal Investigator: Andrea M Haqq, MD, MHS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 12-18 years
2. BMI percentile > 95% for age/sex;
3. Total weight fluctuation over past 6 months < 10%;
4. HOMA-IR > 3.16;
5. FH of T2DM (first or second-degree relative).

Exclusion Criteria:

1. Current use of insulin or diagnosis of T2DM;
2. Systolic or diastolic blood pressure (BP) > 99th percentile for age and sex;
3. Acute infectious or inflammatory condition over the preceding 1 month; hospitalization > 48 hrs;
4. History of chronic disease such as inflammatory bowel disease, chronic severe liver or kidney disease or neurologic disorders;
5. Active malignancy;
6. Concomitant use of medication/investigational drug known to affect body weight in the past year;
7. Antibiotic use in past 60 days; probiotic and/or prebiotic supplements use in the past 30 days; use of lipid-lowering and anti-inflammatory medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MET; MET (850 mg po bid - standard of care) + Fiber placebo daily	Drug: Metformin 850 mg oral tablet bid; MET dose: 500 mg daily, increasing to 500 bid if tolerated after 2 weeks, then increasing again 2 weeks later to 850 mg bid (1700 mg daily).
Active Comparator: FIBER; Fiber supplementation [35g fiber daily] + MET placebo po bid	Dietary supplement: Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.; The first week of treatment will use 1/3 the daily treatment dose; then 2/3 dose for the second and third weeks; then the full dose thereafter, to allow time for adaptation.
Experimental: FIBER + MET; Fiber supplementation [35g fiber daily] + MET 850 mg po bid	Drug: Metformin 850 mg oral tablet bid; MET dose: 500 mg daily, increasing to 500 bid if tolerated after 2 weeks, then increasing again 2 weeks later to 850 mg bid (1700 mg daily).; Dietary supplement: Supplemental fiber mixture (35 g total) composed of 6g of Oligofructose + 12g of resistant maltodextrin + 12g of acacia gum + 5g of PGX.; The first week of treatment will use 1/3 the daily treatment dose; then 2/3 dose for the second and third weeks; then the full dose thereafter, to allow time for adaptation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in HOMA-IR	Change in HOMA-IR value	Baseline, 6, and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in body weight	Body weight measured in kg	Baseline, 6, and 12 months
Changes in body mass index (BMI)	BMI percentile and z-score according to age and sex will be estimated	Baseline, 6, and 12 months
Changes in body composition	Body density using air-displacement plethysmography will be assessed to estimate fat mass and fat-free mass.	Baseline, 6, and 12 months
Changes in inflammation	Markers of inflammation that will be measured are: high-sensitivity C-reactive protein, interleukin, tumor necrosis factor-alpha)	Baseline, 6, and 12 months
Changes in metabolic function	The markers of metabolic function that will be measured are: fasting glucose, lipids (total, high and low density lipoprotein cholesterol; triglycerides), and oral glucose tolerance test.	Baseline, 6, and 12 months
Changes in satiety hormones	Markers of satiety that will be measured are: acylated ghrelin, peptide tyrosine tyrosine, GLP-1, leptin, and adiponectin.	Baseline, 6, and 12 months
Changes in quality of life	Quality of life will be measured by the a questionnaire	Baseline, 6, and 12 months
Changes in perceived hunger and satiety	Perceived hunger and satiety will be assessed by a questionnaire	Baseline, 6, and 12 months
Changes in gut microbiota composition	Fecal microbiota composition will be characterized by 16S rRNA gene amplicons sequencing using taxonomic and non-taxonomic based approaches.	Baseline, 6, and 12 months
Changes in gut microbiome functions	Fecal microbiome functions will be assessed through whole metagenomic sequencing, stool SCFAs and bile acids, and plasma metabolomics.	Baseline, 6, and 12 months
Changes in intestinal barrier integrity	Plasma lipopolysaccharide-binding protein and fecal calprotectin will be determined as measures of gut barrier integrity	Baseline, 6, and 12 months

Collaborators and Investigators

• Sponsor: University of Alberta
• Investigators: Principal Investigator: Andrea M Haqq, MD, MHS, University of Alberta

Publications and helpful links

General Publications

• Deehan EC, Colin-Ramirez E, Triador L, Madsen KL, Prado CM, Field CJ, Ball GDC, Tan Q, Orsso C, Dinu I, Pakseresht M, Rubin D, Sharma AM, Tun H, Walter J, Newgard CB, Freemark M, Wine E, Haqq AM. Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial. Trials. 2021 Feb 17;22(1):148. doi: 10.1186/s13063-021-05060-8.
• Fahim SM, Huey SL, Palma Molina XE, Agarwal N, Ridwan P, Ji N, Kibbee M, Kuriyan R, Finkelstein JL, Mehta S. Gut microbiome-based interventions for the management of obesity in children and adolescents aged up to 19 years. Cochrane Database Syst Rev. 2025 Jul 10;7(7):CD015875. doi: 10.1002/14651858.CD015875.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Estimated): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Metformin; Dietary fiber
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Hyperinsulinism; Overweight; Obesity; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Insulin Resistance; Pediatric Obesity; Organic Chemicals; Carbohydrates; Polymers; Macromolecular Substances; Polysaccharides; Biological Products; Complex Mixtures; Biguanides; Guanidines; Amidines; Biopolymers; Plant Gums; Plant Exudates; Metformin; oligofructose; Gum Arabic
• Other Study ID Numbers: RN. # 414120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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