Author, year | Study design | Study duration | Number of participants enrolled | Mean age (years) | Cognitive outcome | Cognitive diagnosis | Diabetes diagnosis | Intervention group | Control group |
Biemans et al,27
2015 | Cohort | NR | 550 | 61.6 | Alzheimer’s disease (AD) and multi-infarct dementia | ICPC | ICPC | Metformin B12 deficient | Metformin B12 replete |
Bruce et al, 23 2014 | Cohort | 14.7 years | 335 | 57.5 | Cognitive impairment (CI) and dementia | MMSE and CDR | Chart records | Insulin | NR |
Cheng et al,29* 2014 | Cohort | 3.1 years | 5420 | 73.6 | Dementia | ICD-9 | ICD-9 | Metformin, sulfonylurea, thiazolidinedione | NR |
Chin et al,41* 2016 | Cohort | 3.4 years | 1957 | 67.5 | Dementia | HIRAS claim database | HIRAS claim database | No hypoglycemic event, hypoglycemic event, two or more hypoglycemic events | NR |
Chou et al,36* 2017 | Case–control | 5 years | 19 203 | NR | Dementia | ICD-9 | ICD-9 | Pioglitazone (high cumulative dose, long-term use, high daily dose) | No pioglitazone |
Cukierman et al,
2014 | RCT | 6.2 years | 11 685 | 63.4 | CI | NR | NR | Insulin glargine targeting FBG <5.3 | Standard care |
Fei et al,18* 2013 | Cross-sectional | NR | 1109 | NR | All-cause dementia, AD, vascular dementia (VaD) | DSM-IV | WHO and ADA | Insulin | NR |
Feinkohl et al,45
2014 | Cohort | 4 years | 831 | 67.7 | NR | MMSE | NR | Hypoglycemic event | No hypoglycemia |
Ha et al,
2017 | Cohort | 10.5 years | 67 458 | NR | NR | NR | NR | Hypoglycemic event | NR |
Heneka et al,20* 2015 | Cohort | 6 years | 145 928 | NR | NR | NR | NR | Pioglitazones (≥8 calendar quarters and <8 calendar quarters), rosiglitazone, metformin, insulin | No pioglitazone, no piolitazone, no rosiglitazone, no metformin, no insulin |
Hsiao et al,33
2014 | Cohort | NR | 65 620 | NR | NR | NR | NR | Any metformin use, past metformin use, recent metformin use, current metformin use, cumulative use less than 2 years, cumulative use greater than 4 years | NR |
Hsu et al,30* 2011 | Cohort | 7 years | 25 393 | NR | Dementia | ICD-9 | NR | Sulfonylurea, metformin, sulfonylurea and metformin | NR |
Huang et al,24
2014 | Cohort | 10 years | 71 433 | 58.7 | AD | ICD-9 | ICD-9 | Metformin, sulfonylurea, thiazolidinedione, alpha glucosidase inhibitor, insulin | NR |
Isik et al,37
2016 | Cohort | 6 months | 253 | 75.4 | AD | NINDs criteria | Serum glucose | Sitagliptin | No sitagliptin, regular DM meds |
Kuan et al,31* 2017 | Cohort | 12 years | 9302 | 64.7 | Dementia, AD, VaD | ICD-9 | ICD-9 | Metformin | No metformin |
Kuo et al,21* 2015 | Cohort | 11 years | 33 709 | 62.3 | Dementia | ICD-9 | ICD-9 | Insulin use | No insulin use |
Launer et al,
2011 | RCT | 3.33 years | 2977 | 62.3 | NR | NR | NR | Intensive diabetic control target A1c <6%, standard glycemic control A1c target 7% to 7.9% | NR |
Logroscino et al,17
2004 | Cohort | 2 years | 1394 | 74.2 | Cognitive decline | Non-specified cognitive tests | Self-report | Oral antidiabetic agents, insulin, no antidiabetic treatment | NR |
Ma et al,* 2015 | Cohort | 4 years | 8213 | 75.3 | Mild cognitive impairment, dementia, VaD, other cause dementia | Petersen’s classification, NINCDS–ADRDA, DSM-III | Self-report, physician diagnosis of diabetes complication, medical records | Insulin, oral antidiabetic agent | No treatment |
Mehta et al,43
2017 | Cohort | 3.8 years | 53 055 | 75.5 | NR | NR | NR | NR | NR |
Moore et al,28
2013 | Cross-sectional | NR | 104 | 73.8 | NR | NR | NR | Metformin | No metformin |
Murray et al, 2017 | Cohort | 7 years | 1328 | 62.1 | NR | NR | NR | Intensive therapy (A1c<6%), standard therapy A1c 7–7.9% | NR |
Naharci et al,34
2016 | Cohort | NR | 1221 | 75.6 | Dementia | NR | NR | Metformin | No metformin |
Ng et al,35
2014 | Cohort | 4 years | 365 | 67 | NR | NR | NR | Metformin use <6 years, metformin use >6 years | NR |
Orkaby et al,32
2017 | Cohort | 5 years | 42 651 | 73.5 | Dementia, AD, VaD | ICD-9 | NR | Metformin, metformin, and sulfonylurea | Sulfonylurea |
Ott et al,15* 1999 | Cohort | 2.1 years | 6370 | 80.6 | Dementia, AD, VaD | DSM, NINCDS | NR | No drug, oral medication, insulin | NR |
Ott et al,16
1996 | Cross-sectional | NR | 6330 | 69.3 | AD and VaD | DSM and ADNI criteria Screen with MMSE or Geriatric Mental State Schedule followed by physician interview and brain imaging | Use of antidiabetic medication or blood glucose >11 | No drug, oral medication, insulin | NR |
Parikh et al,13* 2011 | Cohort | 2 years | 377 838 | 75.5 | Dementia | ICD-9-CM | ICD-9-CM | Insulin, oral antidiabetic agent | NR |
Plastino et al,22
2010 | Cohort | 1 year | 104 | 76.2 | AD | DSM-IV | Use of antidiabetic medication or blood glucose >11 | Oral agents only, insulin plus oral agents | NR |
Rhee et al, 2014 | Cohort | 3.4 years | 1957 | NR | NR | NR | NR | Hypoglycemic event | NR |
Sato et al, 2011 | RCT | 6 months | 42 | 77.4 | NR | NINCDS, CDR score 0.5 or 1 | DM drug Rx or elevated FBG | Pioglitazone in addition to use antidiabetic medications | No pioglitazone only regular antidiabetic medications |
Trento et al, 2015 | Cohort | 8 years | 498 | 66.8 | NR | NR | NR | Insulin | No insulin |
Whitmer et al,25
2013 | Cohort | 5 years | 14 891 | NR | NR | NR | NR | Metformin, sulfonylurea, thiazolidinedione, insulin | SU acted as reference |
Whitmer et al,40* 2009 | Cohort | 3.8 years | 16 667 | 66.3 | Dementia, AD, VaD | ICD-9 | Medical records, pharmacy Rx | One, two, or three episodes of severe hypoglycemia requiring hospital | NR |
Yaffee et al,* 2013 | Cohort | 12 years | 783 | 74.6 | NR | ICD-9 | Self-report, antidiabetic medication, elevated FBG according to ADA criteria | Hypoglycemic event | No hypoglycemic event |
Yuan et al, 2015 | Cohort | 2 years | NR | NR | NR | Self-report, diagnosis codes in Medicare claims, dementia drug use | NR | Metformin, thiazolidinedione, insulin | NR |
Zullo et al,38
2017 | Cohort | NR | 2016 | NR | NR | 1-point increase in MDS Cognitive Performance Scale score | NR | DPP-4 inhibitor | SU |
indicates the study was included within meta-analysis.
ADA, Alzheimer’s Disease Association; ADNI, Alzheimer’s Disease Neuroimaging Initiative; CDR, Clinical Dementia Rating; DPP-4, dipeptidyl peptidase-4; DSM, Diagnostic and Statistical Manual; FBG, fasting blood glucose; HIRAS, Health Insurance Review and Assessment Service; ICD, Internal Classification of Diseases; ICPC, International Classification of Primary Care; MDS, minimum data set; MMSE, Mini-Mental State Examination; NINCDS–ADRDA, National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association; NINDS, National Institute of Neurological Disorders and Stroke; NR, not reported; RCT, randomized controlled trial; SU, sulfonylurea.