Diabetes Mellitus Type 2
Conditions
Keywords
microbiome, metformin, diabetes, polyherbal formulation
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
Interventions
DIETARY_SUPPLEMENTPolyherbal 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).
OTHERPlacebo
Type: Placebo Comparator Description: A placebo formulation that matches PHF in appearance, texture, and administration schedule. Administration: Oral, daily dosage as per study protocol.
DRUGMetformin (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.
Sponsors
Pauls Stradins Clinical University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
25 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycemic Control (HbA1c Levels) | Baseline, Week 24, Week 48 | Measurement of HbA1c (%) to evaluate the impact of PHF on glycemic control compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal Tolerability of Metformin | 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. |
| Fasting and Postprandial Blood Glucose Levels | Baseline, Week 24, Week 48 | Measurement of fasting and postprandial glucose levels using standard biochemical assays. Unit of Measure: mmol/L |
| Time in Range (TIR) Measured by Continuous Glucose Monitoring (CGM) | 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). |
| Relative Abundance of Key Bacterial Taxa in Gut Microbiota | 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. |
| Patient-Reported Outcomes on Quality of Life | 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. |
| Metabolomic Analysis of Stool Samples (Amino acids) | 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). |
| Metabolomic Analysis of Stool Samples (Bile acids) | 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). |
| Metabolomic Analysis of Stool Samples (Short-chain fatty acids (SCFAs)) | 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). |
Countries
Latvia
Outcome results
None listed