Background: Cognitive deficits differentially affect individuals with type 2 diabetes mellitus (T2DM) and
mood disorders. Accumulating evidence implicates disturbances in metabolism as salient to cognitive function. Thus, the
mitigation of metabolic disturbances may preserve or ameliorate cognitive function. This review aims to evaluate
available evidence investigating the effects of metformin on cognitive function as well as summarize putative mechanistic
properties related to these clinical effects.
Methods: A PubMed search was conducted using the search words including, but not limited to: metformin, Major
Depressive Disorder, type 2 diabetes mellitus, and cognitive dysfunction. All English language articles published from
1990 to July 2014 were reviewed.
Results: Extant preclinical and clinical data have been mixed, wherein both cognitive disruption and pro-cognitive effects
have been reported with the administration of metformin. Sound mechanistic evidence supports metformin as a treatment;
however, the heterogeneity of study designs has contributed to an inability to arrive at an unequivocal conclusion
regarding metformin effects upon cognition.
Conclusion: Available evidence does not provide a robust signal for improvement in cognition in either mood disorder or
T2DM samples. Notwithstanding, it is premature to label metformin as a “no-go” agent for further testing and
development for cognitive dysfunction. A well designed, proof-of-concept trial of metformin investigating its possible
cognitive effects in mood disorders is therefore warranted.