This pilot, genotype-stratified clinical trial aims to investigate the safety and preliminary efficacy of berberine supplementation in adult patients with type 2 diabetes mellitus (T2DM) who carry a specific high-risk TCF7L2 polymorphism (e.g., rs7903146) in the homozygous state. The study will compare improvements in glycemic control and metabolic markers between two groups: (1) homozygous carriers of the TCF7L2 "unfavorable" variant and (2) non-carriers (wild-type). It is hypothesized that berberine will yield greater reductions in HbA1c and fasting plasma glucose among homozygous carriers, potentially due to their distinct TCF7L2-mediated insulin secretion and sensitivity pathways.

Type 2 diabetes mellitus is driven by a combination of insulin resistance and impaired insulin secretion. Genetic polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been strongly associated with an increased risk of T2DM, potentially through altered beta-cell function and incretin signaling. Berberine, a natural alkaloid derived from plants such as Coptis chinensis, has demonstrated hypoglycemic effects by modulating pathways like AMPK, thereby improving insulin sensitivity and glucose metabolism. This pilot trial aims to clarify whether berberine offers a more pronounced metabolic benefit to individuals homozygous for a "high-risk" TCF7L2 polymorphism by targeting their unique pathophysiological mechanisms. Results will inform future larger-scale, genotype-focused interventional trials.

Inclusion Criteria:

• Adults (age 30-70 years) with a confirmed diagnosis of type 2 diabetes mellitus.
• On stable doses of metformin or other standard oral antihyperglycemic agents for at least 4 weeks prior to enrollment.
• Willingness to undergo genetic testing for TCF7L2 polymorphisms. For the Homozygous Variant Cohort: confirmed homozygous high-risk TCF7L2 polymorphism (e.g., rs7903146) prior to enrollment.
• For the Non-Variant Cohort: confirmed wild-type TCF7L2 genotype.

Exclusion Criteria:

• Current use of insulin therapy or recent (within 4 weeks) change in diabetic medications.

Known hypersensitivity or intolerance to berberine or related compounds.

• Significant renal or hepatic impairment.
• Pregnancy or breastfeeding.
• Any other acute or chronic condition that, in the investigator's judgment, could compromise the patient's safety or the study's integrity.