Essential micronutrients and biguanides (metformin) synergistic and antagonistic interactions on neurocognitive outcomes in type two diabetes mellitus: a systematic review of preclinical and clinical evidence

Most (75%) of the studies showed a synergistic interaction between biguanides (metformin) and micronutrients save a few that showed antagonistic interaction. Integrating micronutrient supplementation particularly vitamin D, zinc, and antioxidant compounds into T2DM management enhances both metabolic control and cognitive function. These findings support a paradigm shift toward combined nutraceutical-pharmacologic therapy within clinical and public health frameworks. Future research should focus on dose optimization, mechanistic validation, and long-term clinical evaluation to develop evidence-based, nutrition-sensitive diabetes care models.