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Metformin may worsen cognitive performance in patients with diabetes
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The use of metformin appeared to be associated with impaired cognitive performance in patients with diabetes, according to researchers.
To investigate the link between metformin, serum vitamin B12, calcium supplementation and cognitive impairment, Eileen M. Moore, PhD, from the University of Melbourne in Australia, and colleagues evaluated participants in the Prospective Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle study of aging and patients from the Barwon region of southeastern Australia through the Cognitive Dementia and Memory Services clinic at the McKellar Centre. Patients with Alzheimer’s disease or mild cognitive impairment and those who were cognitively intact were included in the study.
Eileen M. Moore
Using the Mini-Mental State Examination (MMSE), researchers categorized patients (aged 51 to 99 years; 59.5% women) into four levels of cognition: most impaired (MMSE <18), mildly impaired (MMSE 18-23), minimally impaired (MMSE 24-27) and not impaired (MMSE 28-30).
According to data, of 1,354 patients included in the analysis, 10.1% scored less than 18 on the MMSE, 17.7% were mildly impaired, 21.8% were minimally impaired and 50.4% were not impaired. Researchers reported that patients with type 2 diabetes (n=126) displayed worse cognitive performance compared with patients who did not have diabetes (n=1,228; adjusted OR=1.51; 95% CI, 1.03-2.21). Additional data indicate that, among those with diabetes, cognitive performance was worse in patients who were being treated with metformin compared with those who were not (OR=2.23; 95% CI, 1.05-4.75). Cognitive performance was also worse among patients with diabetes who had vitamin B12 levels <250 pmol/L (adjusted OR=2.29; 95% CI, 1.12-4.66), researchers wrote.
However, after adjustment for age, sex, level of education, history of depression, serum vitamin B12 and metformin use, patients with diabetes who were taking calcium supplements displayed better cognitive performance (adjusted OR=0.41; 95% CI, 0.19-0.92), they wrote.
“We recommend a larger study to examine the effect of dose and duration of metformin use, and the effects of other antidiabetic agents using a battery of cognitive assessments and following participants over a number of years,” researchers wrote.
Disclosure: See the study for a full list of disclosures.
Perspective
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Suneil Koliwad, MD, PhD
If you take the caveats along with the interesting link that the authors have established, the researchers do a service to clinicians and the scientific community by bringing up new associations that people may not have thought of before. My hope is that these associations will stimulate this group and/or other researchers to perform properly controlled, prospective studies analyzing both short- and long-term risks of diabetes and the use of metformin in terms of cognitive performance and mood.
Perhaps, as scientists also begin to think about potential mechanisms by which vitamin B12 and metformin exert their effects in the brain in this regard, there may be more mechanistic studies that can be done in both humans and model organisms that could really shed light on how these associations work if they are indeed proved to be true prospectively.
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