Metformin’s Effects on Cognitive Function from a Biovariance Perspective: A Narrative Review

This study examines the effects of metformin on brain functions focusing on the variability of the results reported in the literature. While some studies suggest that metformin may have neuroprotective effects in diabetic patients, others report an insignificant impact of metformin on cognitive function, or even a negative effect. We propose that this inconsistency may be due to intrinsic cellular-level variability among individuals, which we term "biovariance". Biovariance persists even in demographically homogeneous samples due to complex and stochastic biological processes. Additionally, the complex metabolic actions of metformin, including its influence on neuroenergetics and neuronal survival, may produce different effects depending on individual metabolic characteristics.