Diabetes Mellitus Type 2MetherbNCT06846138
Enhancing the Efficacy and Tolerability of Metformin by add-on Polyherbal Formulation: a Gut Microbiome Study
A study testing Polyherbal Formulation (PHF) and Metformin (Standard Treatment for Type 2 Diabetes) in people with Diabetes Mellitus Type 2, run by Pauls Stradins Clinical University Hospital at 1 site in Latvia.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Diabetes Mellitus Type 2
- What is being tested?
- Polyherbal Formulation (PHF) and Metformin (Standard Treatment for Type 2 Diabetes)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteLatvia
- Study dates
- 1 Mar 2025to 1 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this 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
- Conditions
- Diabetes Mellitus Type 2
- Being tested
- Polyherbal Formulation (PHF), Placebo, Metformin (Standard Treatment for Type 2 Diabetes)
- Keywords
- microbiome, metformin, diabetes, polyherbal formulation
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Polyherbal formulation | Experimental | Participants in this arm will receive an add-on polyherbal formulation (PHF). Treatment Duration: 24 weeks, followed by a crossover to the placebo arm. Receives: Dietary Supplement: Polyherbal Formulation (PHF); Drug: Metformin (Standard Treatment for Type 2 Diabetes) |
| Placebo | Placebo comparator | Participants in this arm will receive a placebo. Treatment Duration: 24 weeks, followed by a crossover to the PHF arm. Receives: Other: Placebo; Drug: Metformin (Standard Treatment for Type 2 Diabetes) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glycemic Control (HbA1c Levels)
Measurement of HbA1c (%) to evaluate the impact of PHF on glycemic control compared to placebo.
Measured: Baseline, Week 24, Week 48
Secondary outcomes (8)
Relative Abundance of Key Bacterial Taxa in Gut Microbiota
Description: Measurement of the relative abundance of specific bacterial taxa (Akkermansia muciniphila, Escherichia spp., Intestinibacter) in fecal samples using metagenomic sequencing.
Measured: Baseline, Week 2, Week 24, Week 25, Week 48
Gastrointestinal Tolerability of Metformin
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.
Measured: Baseline, Week 2, Week 24, Week 25, Week 48
Fasting and Postprandial Blood Glucose Levels
Measurement of fasting and postprandial glucose levels using standard biochemical assays.
Unit of Measure: mmol/L
Measured: Baseline, Week 24, Week 48
Time in Range (TIR) Measured by Continuous Glucose Monitoring (CGM)
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).
Measured: Week 1
Metabolomic Analysis of Stool Samples (Short-chain fatty acids (SCFAs))
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).
Measured: Baseline, Week 24, Week 48
Patient-Reported Outcomes on Quality of Life
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.
Measured: Baseline, Week 24, Week 48
Metabolomic Analysis of Stool Samples (Amino acids)
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).
Measured: Baseline, Week 24, Week 48
Metabolomic Analysis of Stool Samples (Bile acids)
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).
Measured: Baseline, Week 24, Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2025
- Study start1 Mar 2025
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pauls Stradins Clinical University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Valdis Pirags, Pauls Stradins Clinical University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06846138
- Sponsor's protocol ID
- lzp-2023/1-0422
- Other IDs
- lzp-2023/1-0422
- Acronym
- Metherb
- Status last verified
- Jul 2025
- First submitted
- 7 Feb 2025
- Last updated
- 17 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing the Efficacy and Tolerability of Metformin by add-on Polyherbal Formulation: a Gut Microbiome Study
- ClinicalTrials.gov ID
- NCT06846138
- Acronym / sponsor ID
- Metherb / lzp-2023/1-0422
- Conditions
- Diabetes Mellitus Type 2
- Keywords
- microbiome, metformin, diabetes, polyherbal formulation
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Pauls Stradins Clinical University HospitalUniversity, hospital or other
- Study start
- 1 Mar 2025 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 25 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Polyherbal formulation | Experimental | Dietary Supplement: Polyherbal Formulation (PHF), Drug: Metformin (Standard Treatment for Type 2 Diabetes)Participants in this arm will receive an add-on polyherbal formulation (PHF). Treatment Duration: 24 weeks, followed by a crossover to the placebo arm. |
| Placebo | Placebo comparator | Other: Placebo, Drug: Metformin (Standard Treatment for Type 2 Diabetes)Participants in this arm will receive a placebo. Treatment Duration: 24 weeks, followed by a crossover to the PHF arm. |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (10 listed)
- Type 1 Diabetes Mellitus Current or recent (last 6 months) use of polyherbal formulations (PHF) Pregnancy or breastfeeding
- Diabetic ketoacidosis Proliferative retinopathy Chronic kidney disease Stage IIIb or higher (eGFR <45 mL/min/1.73m²)
- Stroke Myocardial infarction Unstable angina Heart failure
- 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)
- Inflammatory bowel disease Chronic diarrhea of unknown origin Severe infection requiring antibacterial therapy Participation in another interventional study within the last 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Polyherbal Formulation (PHF)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). | Dietary supplement | Polyherbal formulation |
| PlaceboType: Placebo Comparator Description: A placebo formulation that matches PHF in appearance, texture, and administration schedule. Administration: Oral, daily dosage as per study protocol. | Other | Placebo |
| Metformin (Standard Treatment for Type 2 Diabetes)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. | Drug | Placebo, Polyherbal formulation |
Primary outcome
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.
8 secondary outcomes
Relative Abundance of Key Bacterial Taxa in Gut Microbiota
Time frame: Baseline, Week 2, Week 24, Week 25, Week 48
Gastrointestinal Tolerability of Metformin
Time frame: Baseline, Week 2, Week 24, Week 25, Week 48
Fasting and Postprandial Blood Glucose Levels
Time frame: Baseline, Week 24, Week 48
Time in Range (TIR) Measured by Continuous Glucose Monitoring (CGM)
Time frame: Week 1
Metabolomic Analysis of Stool Samples (Short-chain fatty acids (SCFAs))
Time frame: Baseline, Week 24, Week 48
Patient-Reported Outcomes on Quality of Life
Time frame: Baseline, Week 24, Week 48
Metabolomic Analysis of Stool Samples (Amino acids)
Time frame: Baseline, Week 24, Week 48
Metabolomic Analysis of Stool Samples (Bile acids)
Time frame: Baseline, Week 24, Week 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2025.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Polyherbal Formulation (PHF) and Metformin (Standard Treatment for Type 2 Diabetes) in people with Diabetes Mellitus Type 2, run by Pauls Stradins Clinical University Hospital at 1 site in Latvia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 17 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Latvia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Glycemic Control (HbA1c Levels) (time frame: Baseline, Week 24, Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2025.