TY - JOUR
T1 - Metformin Use Associated with Reduced Risk of Dementia in Patients with Diabetes
T2 - A Systematic Review and Meta-Analysis
AU - Campbell, Jared M.
AU - Stephenson, Matthew D.
AU - De Courten, Barbora
AU - Chapman, Ian
AU - Bellman, Susan M.
AU - Aromataris, Edoardo
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: Metformin, a first line antihyperglycemic medication, is an AMPK activator and has been hypothesized to act as a geroprotective agent. Studies on its association with various classifications of age-related cognitive decline have shown mixed results with positive and negative findings. Objective: To synthesize the best available evidence on the association of metformin-use with risk, progression, and severity of dementia. Method: Eligible research investigated the effect of metformin on dementia, Alzheimer's disease, or any measure of cognitive impairment compared to any control group who were not receiving metformin. The initial search resulted in 862 citations from which 14 studies (seven cohort, four cross-sectional, two RCTs, and one case control) were included. Results: Meta-analysis of three studies showed that cognitive impairment was significantly less prevalent in diabetic metformin (Odds ratio = 0.55, 95%CI 0.38 to 0.78), while six studies showed that dementia incidence was also significantly reduced (Hazard ratio = 0.76, 95%CI 0.39 to 0.88). Mini-Mental State Examination scores were not significantly affected by metformin-use, although both RCTs showed that metformin had a neuroprotective effect compared to placebo. Some studies found negative or neutral effects for metformin use by people with diabetes; the potential mechanism of metformin-induced vitamin B12 deficiency is discussed. Conclusions: Metformin should continue to be used as a first line therapy for diabetes in patients at risk of developing dementia or Alzheimer's disease. The use of metformin by individuals without diabetes for the prevention of dementia is not supported by the available evidence.
AB - Background: Metformin, a first line antihyperglycemic medication, is an AMPK activator and has been hypothesized to act as a geroprotective agent. Studies on its association with various classifications of age-related cognitive decline have shown mixed results with positive and negative findings. Objective: To synthesize the best available evidence on the association of metformin-use with risk, progression, and severity of dementia. Method: Eligible research investigated the effect of metformin on dementia, Alzheimer's disease, or any measure of cognitive impairment compared to any control group who were not receiving metformin. The initial search resulted in 862 citations from which 14 studies (seven cohort, four cross-sectional, two RCTs, and one case control) were included. Results: Meta-analysis of three studies showed that cognitive impairment was significantly less prevalent in diabetic metformin (Odds ratio = 0.55, 95%CI 0.38 to 0.78), while six studies showed that dementia incidence was also significantly reduced (Hazard ratio = 0.76, 95%CI 0.39 to 0.88). Mini-Mental State Examination scores were not significantly affected by metformin-use, although both RCTs showed that metformin had a neuroprotective effect compared to placebo. Some studies found negative or neutral effects for metformin use by people with diabetes; the potential mechanism of metformin-induced vitamin B12 deficiency is discussed. Conclusions: Metformin should continue to be used as a first line therapy for diabetes in patients at risk of developing dementia or Alzheimer's disease. The use of metformin by individuals without diabetes for the prevention of dementia is not supported by the available evidence.
KW - Alzheimer's disease
KW - cognitive dysfunction
KW - dementia
KW - diabetes mellitus
KW - meta-analysis
KW - metformin
KW - systematic review
UR - http://www.scopus.com/inward/record.url?scp=85054147062&partnerID=8YFLogxK
U2 - 10.3233/JAD-180263
DO - 10.3233/JAD-180263
M3 - Article
C2 - 30149446
AN - SCOPUS:85054147062
SN - 1387-2877
VL - 65
SP - 1225
EP - 1236
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -