Clinical trial NCT06846138: Enhancing the Efficacy and Tolerability of Metformin by add-on Polyherbal Formulation: a Gut Microbiome Study
Official title: Enhancing the Efficacy and Tolerability of Metformin by add-on Polyherbal Formulation: a Gut Microbiome Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Diabetes Mellitus Type 2
Keywords: microbiome
metformin
diabetes
polyherbal formulation
Lead sponsor: Pauls Stradins Clinical University Hospital
Sponsor class: OTHER
First posted: 2025-02-25
Enrollment: 66
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in Glycemic Control (HbA1c Levels)
timeFrame: Baseline, Week 24, Week 48
Secondary outcomes:
measure: Relative Abundance of Key Bacterial Taxa in Gut Microbiota
timeFrame: Baseline, Week 2, Week 24, Week 25, Week 48
measure: Gastrointestinal Tolerability of Metformin
timeFrame: Baseline, Week 2, Week 24, Week 25, Week 48
measure: Fasting and Postprandial Blood Glucose Levels
timeFrame: Baseline, Week 24, Week 48
measure: Time in Range (TIR) Measured by Continuous Glucose Monitoring (CGM)
timeFrame: Week 1
measure: Metabolomic Analysis of Stool Samples (Short-chain fatty acids (SCFAs))
timeFrame: Baseline, Week 24, Week 48
measure: Patient-Reported Outcomes on Quality of Life
timeFrame: Baseline, Week 24, Week 48
measure: Metabolomic Analysis of Stool Samples (Amino acids)
timeFrame: Baseline, Week 24, Week 48
measure: Metabolomic Analysis of Stool Samples (Bile acids)
timeFrame: Baseline, Week 24, Week 48
Other outcomes:
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