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Enrolling by Invitation

NCT Number: NCT06846138

Enhancing the Efficacy and Tolerability of Metformin by add-on Polyherbal Formulation: a Gut Microbiome Study

Study population: Type 2 diabetes patients Design of the study: Randomized, two-arm, placebo-controlled, and prospective crossover cohort study.

Objective: To evaluate the effects of interactions between metformin and traditionally used polyherbal formulations on gut microbiota in a prospective crossover study involving type 2 diabetes mellitus patients.

Sample size: 66 patients. Duration of study: 06/2024 - 12/2026

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Key information

Conditions

Diabetes Mellitus Type 2 Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

25 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Pauls Stradins Clinical University Hospital

Riga, LV-1002, Latvia

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Participants must meet all of the following criteria to be eligible for enrollment:

Clinical diagnosis of Type 2 Diabetes Mellitus (T2D) HbA1c level between 6.5% and 8.5% On a stable dose of oral antidiabetic therapy for at least 6 months Age: ≥ 25 years and ≤ 80 years History of metformin intolerance, defined as previously reported gastrointestinal side effects or inability to tolerate full-dose metformin Willing and able to provide written informed consent Willing to comply with study procedures, including stool sample collection and continuous glucose monitoring (CGM)

Exclusion criteria

Participants will be excluded if they meet any of the following criteria:

Type 1 Diabetes Mellitus Current or recent (last 6 months) use of polyherbal formulations (PHF) Pregnancy or breastfeeding

Severe diabetic complications, such as:

Diabetic ketoacidosis Proliferative retinopathy Chronic kidney disease Stage IIIb or higher (eGFR <45 mL/min/1.73m²)

Recent cardiovascular events (within the last 6 months), including:

Stroke Myocardial infarction Unstable angina Heart failure

Severe systemic disease that could interfere with participation, such as:

Active cancer Severe autoimmune disease Current antibiotic therapy (within 2 months of study enrollment) Use of probiotics or prebiotics (within 1 month of study enrollment)

Severe gastrointestinal conditions, including:

Inflammatory bowel disease Chronic diarrhea of unknown origin Severe infection requiring antibacterial therapy Participation in another interventional study within the last 3 months

Treatment and study plan

Polyherbal Formulation (PHF)

Dietary Supplement

Description: A polyherbal formulation with known beneficial effects on gut microbiota and metabolic regulation. The formulation contains selected plant extracts studied for their hypoglycemic, antioxidant, and gut microbiota-modulating properties.

Administration: Oral, daily dosage as per study protocol. Supplier: Arya Vaidya Pharmacy (AVP), Coimbatore, India (GMP-certified).

Placebo

Other

Type: Placebo Comparator Description: A placebo formulation that matches PHF in appearance, texture, and administration schedule.

Administration: Oral, daily dosage as per study protocol.

Metformin (Standard Treatment for Type 2 Diabetes)

Drug

Description: Metformin is an FDA and EMA-approved antihyperglycemic medication that improves glycemic control by reducing hepatic glucose production and enhancing insulin sensitivity.

Administration: Oral, per standard dosing guidelines. Availability: Provided to all participants per the national reimbursement scheme for T2D patients in Latvia.

Primary outcomes

  1. Change in Glycemic Control (HbA1c Levels)

    Time frame: Baseline, Week 24, Week 48

    Measurement of HbA1c (%) to evaluate the impact of PHF on glycemic control compared to placebo.

Secondary outcomes

  1. Relative Abundance of Key Bacterial Taxa in Gut Microbiota

    Time frame: Baseline, Week 2, Week 24, Week 25, Week 48

    Description: Measurement of the relative abundance of specific bacterial taxa (Akkermansia muciniphila, Escherichia spp., Intestinibacter) in fecal samples using metagenomic sequencing.

  2. Gastrointestinal Tolerability of Metformin

    Time frame: Baseline, Week 2, Week 24, Week 25, Week 48

    Assessment of gastrointestinal side effects, including nausea, bloating, diarrhea, and abdominal discomfort, using a standardized gut microbiota-related symptom questionnaire.

    Scale Name: Gastrointestinal Symptom Rating Scale (GSRS) Score Range: Minimum = 0, Maximum = 4 Interpretation: Lower scores indicate better gastrointestinal tolerability.

  3. Fasting and Postprandial Blood Glucose Levels

    Time frame: Baseline, Week 24, Week 48

    Measurement of fasting and postprandial glucose levels using standard biochemical assays.

    Unit of Measure: mmol/L

  4. Time in Range (TIR) Measured by Continuous Glucose Monitoring (CGM)

    Time frame: Week 1

    Time in Range (TIR) Measured by Continuous Glucose Monitoring (CGM) Description: Measurement of the percentage of time that blood glucose levels remain within the target range (70-180 mg/dL) using data from Continuous Glucose Monitoring (CGM).

  5. Metabolomic Analysis of Stool Samples (Short-chain fatty acids (SCFAs))

    Time frame: Baseline, Week 24, Week 48

    The levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, and caproic acid will be quantified using gas chromatography-mass spectrometry (GC-MS). These concentrations will be reported in micromoles per gram of fecal matter (μmol/g).

  6. Patient-Reported Outcomes on Quality of Life

    Time frame: Baseline, Week 24, Week 48

    Description: Evaluation using a validated diabetes-related quality of life questionnaire. Diabetes Quality of Life (DQOL) Questionnaire.

    Scoring: Items are scored on a 5-point Likert scale, with higher scores typically indicating more negative impacts or dissatisfaction.

  7. Metabolomic Analysis of Stool Samples (Amino acids)

    Time frame: Baseline, Week 24, Week 48

    The following amino acids will be analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS): acetylcarnitine, arginine, butyrylcarnitine, carnitine, citrulline, creatinine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serotonin, taurine, tryptophan, tyrosine, and valine. Results will be expressed in nanomoles per gram of fecal matter (nmol/g).

  8. Metabolomic Analysis of Stool Samples (Bile acids)

    Time frame: Baseline, Week 24, Week 48

    The bile acids to be measured include cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, along with their conjugated forms: glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, taurolithocholic acid, and ursodeoxycholic acid. These will be quantified using liquid chromatography-mass spectrometry (LC-MS), with concentrations reported in micromoles per gram of fecal matter (μmol/g).

Sponsors and collaborators

Lead sponsor

Pauls Stradins Clinical University Hospital

Other

Registry information

Acronym: Metherb

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Feb 25, 2025
Registry last updated
Jul 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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