Metformin use associated with cognitive impairment

Metformin is associated with cognitive impairment in people with type 2 diabetes, but the effect may be mitigated by vitamin B₁₂ and calcium supplements, a new study found.

Australian researchers recruited participants from the Prospective Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a clinic for the elderly, and a private geriatrician's practice. Participants with mild cognitive impairment, those with Alzheimer's disease (AD) or those who were cognitively intact were included; those with stroke or neurodegenerative diseases other than AD were excluded. After exclusions, 1,354 people (mean age, 74 years) were in the final analysis—1,228 with no diabetes, 104 with type 2 diabetes, and 22 with impaired glucose tolerance. Researchers performed subgroup analyses on the latter two groups of participants.

After adjustments for sex, age, depression and education, participants with type 2 diabetes had worse cognitive performance than those without diabetes (adjusted odds ratio [AOR], 1.51; 95% CI, 1.03 to 2.21; P=0.03). Diabetes participants who took metformin had worse cognitive performance than diabetes participants who didn't (AOR, 2.23; 95% CI, 1.05 to 4.75; P=0.04). Diabetes participants who had vitamin B₁₂ levels below 250 ρmol/L also had worse cognitive performance than those whose levels were higher (AOR, 2.29; 95% CI, 1.12 to 4.66).

Each one-year increase in age was associated with an 8% higher risk of decreased cognitive performance. A secondary or tertiary level of education was the greatest predictor of better cognitive performance in diabetes participants. Once adjustments were made for age, sex, depression history, education level, use of serum vitamin B₁₂ and metformin, the diabetic and impaired glucose tolerance participants who took calcium supplements performed better on cognitive measures than those who didn't take them (AOR, 0.41; 95% CI, 0.19 to 0.92; P=0.03). Results were published online Sept. 5 by Diabetes Care.

The researchers noted that there wasn't enough information in their study to determine how duration and dose of metformin, or severity and duration of diabetes, affected results. They pointed out that while calcium supplements seem to be linked to better cognitive outcomes, these supplements also have been associated with higher risk for myocardial infarction in postmenopausal women and in chronic kidney disease patients, and thus their safety still needs to be determined. Vitamin B₁₂ supplements are a promising potential option for people with diabetes who take metformin, they said. The authors conclude by recommending increased monitoring of the cognitive abilities of diabetic patients older than 50 years who take metformin.