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

NCT06846138 | Enrolling By Invitation DMC

• 1 other identifier: lzp-2023/1-0422
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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 involving type 2 diabetes mellitus patients. Sample size: 66 patients. Duration of study: 06/2024 - 12/2026

Conditions

Diabetes Mellitus Type 2

Keywords

microbiome; metformin; diabetes; polyherbal formulation

Outcome Measures

Primary Outcomes (1)

• Change in Glycemic Control (HbA1c Levels)

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

  Baseline, Week 24, Week 48

Secondary Outcomes (8)

• Relative Abundance of Key Bacterial Taxa in Gut Microbiota

  Baseline, Week 2, Week 24, Week 25, Week 48

• Gastrointestinal Tolerability of Metformin

  Baseline, Week 2, Week 24, Week 25, Week 48

• Fasting and Postprandial Blood Glucose Levels

  Baseline, Week 24, Week 48

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

  Week 1

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

  Baseline, Week 24, Week 48

Study Arms (2)

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.

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.

Other: Placebo; Drug: Metformin (Standard Treatment for Type 2 Diabetes)

Interventions

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).

Polyherbal formulation

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.

Placebo

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.

Placebo; Polyherbal formulation

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Pauls Stradins Clinical University Hospital: lead

Study Sites (1)

Pauls Stradins Clinical University Hospital

Riga, LV-1002, Latvia

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: February 7, 2025
• First Posted: February 25, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF

Locations

LA (1)