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

Pauls Stradins Clinical University Hospital

Status: Invitation-only

Conditions: Diabetes Mellitus Type 2

Treatments: Drug: Metformin (Standard Treatment for Type 2 Diabetes); Other: Placebo; Dietary Supplement: Polyherbal Formulation (PHF)

Study type: Interventional

Funder types: Other

Identifiers

NCT06846138

lzp-2023/1-0422 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Enrollment: 66 estimated patients

Sex: All

Ages: 25 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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66 participants in 2 patient groups, including a placebo group

Polyherbal formulation

Experimental group

Description:

Participants in this arm will receive an add-on polyherbal formulation (PHF). Treatment Duration: 24 weeks, followed by a crossover to the placebo arm.

Treatment:

Dietary Supplement: Polyherbal Formulation (PHF)

Drug: Metformin (Standard Treatment for Type 2 Diabetes)

Placebo

Placebo Comparator group

Description:

Participants in this arm will receive a placebo. Treatment Duration: 24 weeks, followed by a crossover to the PHF arm.

Treatment:

Other: Placebo

Drug: Metformin (Standard Treatment for Type 2 Diabetes)