Diabetes Mellitus Type 2, Type 2 Diabetes
Conditions
Keywords
Type 2 diabetes, Type 2 diabetes mellitus, HbA1c, Glycemic response, Glycemic control, Microbiome, Gut microbiome, Nutritional intervention, AI-guided formulation design, Artificial intelligence, Randomized controlled trial, AIM-MET
Brief summary
AIM-MET is a randomized clinical study testing whether a fixed microbiome-targeted nutritional product can improve blood sugar control in adults with type 2 diabetes when used in addition to usual stable diabetes treatment. The study will compare the active nutritional product with a matching placebo over 24 weeks. The product was designed using artificial intelligence before the study began, but the same fixed formulation will be used for all participants assigned to the active group. Artificial intelligence will not be used during the study to make individual treatment decisions, adjust dosing, or personalize the product. The main question is whether participants receiving the active product have a greater reduction in HbA1c, a standard marker of average blood sugar levels, from the start of the study to Week 24 compared with participants receiving placebo. The study will also evaluate early blood sugar changes, fasting glucose, body weight and waist measurements in participants with baseline BMI of at least 25.0 kg/m2, safety, hypoglycaemia events, patient-reported outcomes, and gut microbiome features. This is a 100-participant proof-of-concept study intended to estimate the size of the treatment signal, safety, feasibility, and parameters needed for a future larger confirmatory trial.
Detailed description
Type 2 diabetes is commonly managed with lifestyle measures and glucose-lowering medications, but many individuals continue to have residual hyperglycaemia despite stable treatment. Nutritional interventions that target the gut microbiome may provide a safe adjunctive approach if they can improve glycaemic control without replacing standard diabetes care. The gut microbiome may influence glucose regulation through several biological pathways, including short-chain fatty acid production, bile acid metabolism, intestinal barrier function, low-grade inflammation, incretin signalling, and other host-microbe interactions. These mechanisms provide the rationale for evaluating a microbiome-targeted nutritional intervention in adults with type 2 diabetes. The investigational product is a fixed AI-guided microbiome-targeted nutritional formulation. The artificial intelligence methodology was used before the clinical trial to support formulation design, including ingredient and dose selection from candidate microbiome-active compounds. The output of this process is one fixed formulation that is locked before participant enrolment and is identical for all participants assigned to the active intervention arm. The artificial intelligence system is not used during the trial for participant-level prediction, diagnosis, clinical decision-making, dosing, personalization, or formulation adjustment. Therefore, the clinical study evaluates the fixed nutritional product, not the independent clinical performance of an artificial intelligence system. Participants are randomized in a 1:1 ratio to receive either the active nutritional intervention or a matching placebo for 24 weeks. Both groups receive identical structured lifestyle counselling and continue stable background glucose-lowering therapy as clinically appropriate. The placebo is matched to the active product in appearance, taste, smell, packaging, administration schedule, and storage conditions, and is intended to be microbiome- and glycaemia-neutral. The primary clinical assessment is the change in HbA1c from baseline to Week 24. Week 24 was selected because HbA1c reflects average glycaemia over the preceding 2 to 3 months and is therefore appropriate for evaluating a gradually acting nutritional and microbiome-targeted intervention. The study also evaluates supportive glycaemic, anthropometric, safety, patient-reported, and microbiome-related measures. This 100-participant proof-of-concept trial is designed to detect a clinically meaningful HbA1c signal and to estimate safety, feasibility, variability, and effect-size parameters for a future larger confirmatory trial. The study is not intended to replace standard diabetes care or to assess the investigational product as a substitute for clinically indicated glucose-lowering medication.
Interventions
DIETARY_SUPPLEMENTMicrobiome-targeted oral food supplement
Fixed AI-guided microbiome-targeted oral food supplement administered for 24 weeks. The formulation is fixed and identical for all participants randomized to the active intervention arm. The artificial intelligence methodology was used before the trial for formulation design only and is not used during the trial for participant-level prediction, dosing, clinical decision-making, or formulation adjustment. Participants also receive identical structured lifestyle counselling and continue stable permitted background glucose-lowering therapy as clinically appropriate.
DIETARY_SUPPLEMENTMatching placebo oral supplement
Matching placebo oral supplement administered for 24 weeks. The placebo is matched to the active product in appearance, taste, smell, packaging, administration schedule, and storage conditions. The placebo is intended to be microbiome- and glycaemia-neutral and free of active prebiotic, probiotic, synbiotic, postbiotic, glycaemically active, or other bioactive components reasonably expected to affect HbA1c, fasting plasma glucose, body weight, microbiome composition, or inflammatory markers. Participants also receive identical structured lifestyle counselling and continue stable permitted background glucose-lowering therapy as clinically appropriate.
Sponsors
ENBIOSIS BIOTECHNOLOGIES
Bakırçay University, Faculty of Medicine
Aydin Adnan Menderes University
Buca Seyfi Demirsoy State Hospital
Izmir University of Economics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, care providers, investigators, and outcome assessors remain masked to allocation throughout the 24-week treatment period. Laboratory staff performing primary and key secondary outcome assessments and the statistician performing the primary analysis remain masked until database lock and locking of the Statistical Analysis Plan-defined primary analysis. Active intervention and placebo are matched for appearance, taste, smell, packaging, administration schedule, and storage conditions. Emergency unblinding is permitted only when knowledge of allocation is essential for participant management.
Intervention model description
Participants are randomized 1:1 to active intervention or matching placebo for 24 weeks. Both arms receive identical structured lifestyle counselling and continue stable permitted background glucose-lowering therapy as clinically appropriate. Randomization is stratified by sex, baseline HbA1c category, baseline SGLT2 inhibitor use, and baseline BMI category.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Adults aged 18 to 65 years. Established diagnosis of type 2 diabetes mellitus documented in the medical record, supported by American Diabetes Association diagnostic criteria on at least one prior occasion. HbA1c 6.8% to 8.2% at screening, measured by an NGSP-certified central laboratory assay; confirmed on a repeat sample if discordant with prior records or if the screening value is at the upper or lower boundary. Body mass index 18.5 to 40.0 kg/m2 at screening. Stable background glucose-lowering therapy for at least 3 months before randomization, restricted to metformin, a DPP-4 inhibitor, and/or an SGLT2 inhibitor, either alone or in combination. Documented body-weight stability, defined as no more than +/-5% or +/-3 kg, whichever is smaller, self-reported body-weight change during the 3 months before screening. Willing and able to provide written informed consent. Willing and able to comply with trial visits, study product use, fasting blood sampling, stool sampling, and the study assessment schedule. Willing to receive standardized lifestyle counselling during the 24-week blinded period and to maintain stable background diabetes management as clinically directed. No systemic antibiotic use within 8 weeks before randomization. No probiotic, prebiotic, synbiotic, or postbiotic supplement use within 8 weeks before randomization. Stable hypertension, dyslipidaemia, and stable thyroid replacement therapy are permitted if medication has been initiated and the dose unchanged for at least 3 months before randomization.
Exclusion criteria
Type 1 diabetes, latent autoimmune diabetes of adults, pancreatogenic diabetes, maturity-onset diabetes of the young, gestational diabetes as the current diagnosis, or any non-type-2 form of diabetes. HbA1c less than 6.8% or greater than 8.2% at screening. Current use of GLP-1 receptor agonists or GLP-1/GIP co-agonists, or use within 12 months before randomization. Current use of basal, prandial, or premixed insulin, or any insulin use within 6 months before randomization. Current use of sulfonylureas or meglitinides, or use within 3 months before randomization. Current use of anti-obesity pharmacotherapy or use within 6 months before randomization, including orlistat, naltrexone/bupropion, phentermine/topiramate, or other agents with a primary anti-obesity indication. Recurrent severe hypoglycaemia or hypoglycaemia unawareness. Planned initiation or dose escalation of glucose-lowering medication, anti-obesity medication, or systemic corticosteroids during the 24-week trial period in the judgment of the treating clinician. History of bariatric surgery at any time. Gastrointestinal surgery other than appendectomy or uncomplicated cholecystectomy. Active inflammatory bowel disease, coeliac disease, microscopic colitis, chronic pancreatitis, malabsorption syndrome, or chronic severe gastrointestinal disease likely to affect absorption or trial adherence. Acute gastroenteritis within 4 weeks before randomization. Colonoscopy bowel preparation within 12 weeks before randomization. Faecal microbiota transplantation within 12 months before randomization. Active or recent malignancy within 6 months, except adequately treated non-melanoma skin cancer. Stage 3b to 5 chronic kidney disease, defined as estimated glomerular filtration rate less than 45 mL/min/1.73 m2. Decompensated liver disease or Child-Pugh class B/C. ALT or AST greater than 3 times the upper limit of normal at screening, unless judged clinically insignificant and approved by the investigator. Known or suspected haemoglobinopathy that materially distorts HbA1c measurement or haemoglobin variant known to interfere with the central laboratory assay. Blood transfusion, significant blood loss greater than 250 mL, or erythropoiesis-stimulating agent therapy within 3 months before randomization. Untreated overt thyroid disease, or thyroid medication initiation or dose change within 3 months before randomization. Use of systemic corticosteroids within 4 weeks before randomization. Use of immunosuppressive medication or biologic/immunomodulatory therapy within 5 half-lives before randomization. Pregnancy or lactation; women of childbearing potential not willing to use effective contraception during the 24-week blinded period. Severe psychiatric illness or cognitive impairment that may compromise informed consent, safety, or adherence. Active eating disorder, defined operationally as a positive SCOFF screen with at least 2 affirmative responses at screening, or clinical diagnosis of anorexia nervosa, bulimia nervosa, or binge-eating disorder. Heavy alcohol use or active substance use disorder. Current very-low-calorie diet, ketogenic diet, medically supervised weight-loss diet, or other highly restrictive diet that excludes major food groups. Current cigarette smoking with intention to attempt cessation during the 24-week trial period; current users of nicotine-replacement or smoking-cessation pharmacotherapy initiated within 3 months before randomization. Participation in another interventional clinical trial within 30 days before screening. Known hypersensitivity or clinically significant intolerance to any component of the active product or placebo. Inability or unwillingness to provide stool samples. Any condition that, in the investigator's opinion, would compromise participant safety or trial integrity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c from baseline to Week 24 | Baseline to Week 24 | HbA1c is a blood test that reflects average blood glucose levels over approximately the previous 2 to 3 months. HbA1c is measured using an NGSP-certified central laboratory assay and reported as a percentage. The outcome is the absolute change in HbA1c, in percentage points, from baseline to Week 24. A greater reduction indicates improved glycaemic control. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving HbA1c reduction of at least 0.5 percentage points at Week 24 | Baseline to Week 24 | This outcome measures the proportion of participants whose HbA1c decreases by at least 0.5 percentage points from baseline to Week 24. HbA1c is a blood test reflecting average glucose levels over approximately 2 to 3 months and is measured using an NGSP-certified central laboratory assay. Participants who meet or exceed this reduction threshold are counted as responders. |
| Proportion of participants achieving HbA1c reduction of at least 0.3 percentage points at Week 24 | Baseline to Week 24 | This outcome measures the proportion of participants whose HbA1c decreases by at least 0.3 percentage points from baseline to Week 24. HbA1c is measured using an NGSP-certified central laboratory assay and reported as a percentage. Participants who meet or exceed this reduction threshold are counted as responders. |
| Change in HbA1c from baseline to Week 12 | Baseline to Week 12 | HbA1c is a blood test that reflects average blood glucose levels over approximately the previous 2 to 3 months. This outcome measures the absolute change in HbA1c, in percentage points, from baseline to Week 12. This earlier time point is used to describe the early trajectory of glycaemic response. |
| Change in fasting plasma glucose from baseline to Week 24 | Baseline to Week 24 | Fasting plasma glucose is a blood measure of glucose concentration after an overnight fast of at least 8 hours. Baseline and Week 24 values are each defined as the mean of two fasting plasma glucose samples drawn within a 7-day window. The outcome is the absolute change from baseline to Week 24. A greater reduction indicates improved fasting glycaemia. |
| Achievement of HbA1c less than 7.0% at Week 24 among participants with baseline HbA1c at least 7.0% | Baseline to Week 24 | This outcome measures the proportion of participants with baseline HbA1c of at least 7.0% who achieve HbA1c less than 7.0% at Week 24. HbA1c is measured using an NGSP-certified central laboratory assay and reported as a percentage. Participants below the 7.0% threshold at Week 24 are counted as achieving this outcome. |
| Percent change in body weight at Week 24 in participants with baseline BMI at least 25.0 kg/m2 | Baseline to Week 24 | This outcome is assessed only in participants with baseline body mass index, or BMI, of at least 25.0 kg/m2. Body weight is measured using a standardized calibrated scale procedure. Percent change is calculated as 100 x (Week 24 body weight - baseline body weight) / baseline body weight. A negative value indicates weight reduction. |
| Change in waist circumference at Week 24 in participants with baseline BMI at least 25.0 kg/m2 | Baseline to Week 24 | This outcome is assessed only in participants with baseline BMI of at least 25.0 kg/m2. Waist circumference is measured using a standardized non-stretch tape procedure. The outcome is the absolute change in waist circumference from baseline to Week 24, reported in centimeters. A negative value indicates a reduction in waist circumference. |
Countries
Turkey (Türkiye)
Contacts
CONTACTVarol TUNALI, Dr.
CONTACTBuğra Yağmur, Mr
STUDY_CHAIREngin Güney, Prof. Dr.
Aydın Adnan Menderes University Faculty of Medicine Endocrinology Department
PRINCIPAL_INVESTIGATORVarol Tunali, Dr.
Enbiosis Biotechnology Limited
Outcome results
None listed