AIM-MET: AI-Guided Microbiome-Targeted Nutrition for Glycemic Improvement in Type 2 Diabetes

Exclusion Criteria33

• 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.