Berberine

A landmark 2008 RCT demonstrated that 1500mg/day matched metformin's glycemic control in type 2 diabetes, achieving a 0.8% reduction in HbA1c over three months. This AMPK-mediated cascade inhibits mTOR, reduces IGF-1, enhances autophagy, and improves insulin sensitivity, as detailed in a 2021 *Ageing Research Reviews* analysis. However, bioavailability from standard HCl is only ~5%, so combining with dietary fat and cycling two weeks on, one week off maximizes efficacy. Interactions with CYP3A4-metabolized drugs warrant caution.