Association of Metformin with Better Cognitive Function

Metformin as a Tool to Target Aging, 2016

Emerging evidence suggests that metformin may preserve cognitive function. In the Singapore Longitudinal Aging Study, metformin use was associated with a
51 percent reduced risk of cognitive impairment (defined by modified Mini-Mental Status Exam score percentage 23), which remained robust to adjustment for vascular and
non-vascular risk factors.

Further, the lowest risk was seen in those with longer-term (> 6 years) metformin use (Ng et al., 2014). A large observational study of metformin-treated T2DM patients reported lower rates of dementia than in those treated with other diabetes medications (Cheng et al., 2014). One study suggested that T2DM patients treated with metformin had increased risk for poor cognitive performance (Moore et al., 2013); however, it had a number of methodological flaws (Alagiakrishnan et al., 2013) and has not been replicated.

In one small clinical trial, T2DM patients with depression (n = 58) were treated with metformin or placebo for 24 weeks (Guo et al., 2014). The metformin group showed improved cognitive performance and reduced depressive symptoms, concurrent with improved glycemic control.

In an unpublished trial, non-diabetic subjects (n = 80) with mild cognitive impairment showed significant improvements in some cognitive domains
after 12 months of metformin treatment (Luchsinger et al., 2016). No definitive trials have been conducted.