Table 1*

Characteristics of included studies

Author,
year
Study designStudy durationNumber of participants enrolledMean age (years)Cognitive outcomeCognitive diagnosisDiabetes diagnosisIntervention
group
Control group
Biemans et al,27
2015
CohortNR55061.6Alzheimer’s disease (AD) and multi-infarct dementiaICPCICPCMetformin B12 deficientMetformin B12 replete
Bruce et al, 23 2014Cohort14.7 years33557.5Cognitive impairment (CI) and dementiaMMSE and CDRChart recordsInsulinNR
Cheng et al,29*
2014
Cohort3.1 years542073.6DementiaICD-9ICD-9Metformin, sulfonylurea, thiazolidinedioneNR
Chin et al,41*
2016
Cohort3.4 years195767.5DementiaHIRAS claim databaseHIRAS claim databaseNo hypoglycemic event, hypoglycemic event, two or more hypoglycemic eventsNR
Chou et al,36*
2017
Case–control5 years19 203NRDementiaICD-9ICD-9Pioglitazone (high cumulative dose, long-term use, high daily dose)No pioglitazone
Cukierman et al,
2014
RCT6.2 years11 68563.4CINRNRInsulin glargine targeting FBG <5.3Standard care
Fei et al,18*
2013
Cross-sectionalNR1109NRAll-cause dementia, AD, vascular dementia (VaD)DSM-IVWHO and ADAInsulinNR
Feinkohl et al,45
2014
Cohort4 years83167.7NRMMSENRHypoglycemic eventNo hypoglycemia
Ha et al,
2017
Cohort10.5 years67 458NRNRNRNRHypoglycemic eventNR
Heneka et al,20*
2015
Cohort6 years145 928NRNRNRNRPioglitazones (≥8 calendar quarters and <8 calendar quarters), rosiglitazone, metformin, insulinNo pioglitazone, no piolitazone, no rosiglitazone, no metformin, no insulin
Hsiao et al,33
2014
CohortNR65 620NRNRNRNRAny metformin use, past metformin use, recent metformin use, current metformin use, cumulative use less than 2 years, cumulative use greater than 4 yearsNR
Hsu et al,30*
2011
Cohort7 years25 393NRDementiaICD-9NRSulfonylurea, metformin, sulfonylurea and metforminNR
Huang et al,24
2014
Cohort10 years71 43358.7ADICD-9ICD-9Metformin, sulfonylurea, thiazolidinedione, alpha glucosidase inhibitor, insulinNR
Isik et al,37
2016
Cohort6 months25375.4ADNINDs criteriaSerum glucoseSitagliptinNo sitagliptin, regular DM meds
Kuan et al,31*
2017
Cohort12 years930264.7Dementia, AD, VaDICD-9ICD-9MetforminNo metformin
Kuo et al,21*
2015
Cohort11 years33 70962.3DementiaICD-9ICD-9Insulin useNo insulin use
Launer et al,
2011
RCT3.33 years297762.3NRNRNRIntensive diabetic control target A1c <6%, standard glycemic control A1c target 7% to 7.9%NR
Logroscino et al,17
2004
Cohort2 years139474.2Cognitive declineNon-specified cognitive testsSelf-reportOral antidiabetic agents, insulin, no antidiabetic treatmentNR
Ma et al,*
2015
Cohort4 years821375.3Mild cognitive impairment, dementia, VaD, other cause dementiaPetersen’s classification, NINCDS–ADRDA, DSM-IIISelf-report, physician diagnosis of diabetes complication, medical recordsInsulin, oral antidiabetic agentNo treatment
Mehta et al,43
2017
Cohort3.8 years53 05575.5NRNRNRNRNR
Moore et al,28
2013
Cross-sectionalNR10473.8NRNRNRMetforminNo metformin
Murray et al,
2017
Cohort7 years132862.1NRNRNRIntensive therapy (A1c<6%), standard therapy A1c 7–7.9%NR
Naharci et al,34
2016
CohortNR122175.6DementiaNRNRMetforminNo metformin
Ng et al,35
2014
Cohort4 years36567NRNRNRMetformin use <6 years, metformin use >6 yearsNR
Orkaby et al,32
2017
Cohort5 years42 65173.5Dementia, AD, VaDICD-9NRMetformin, metformin, and sulfonylureaSulfonylurea
Ott et al,15*
1999
Cohort2.1 years637080.6Dementia, AD, VaDDSM, NINCDSNRNo drug, oral medication, insulinNR
Ott et al,16
1996
Cross-sectionalNR633069.3AD and VaDDSM and ADNI criteria Screen with MMSE or Geriatric Mental State Schedule followed by physician interview and brain imagingUse of antidiabetic medication or blood glucose >11No drug, oral medication, insulinNR
Parikh et al,13*
2011
Cohort2 years377 83875.5DementiaICD-9-CMICD-9-CMInsulin, oral antidiabetic agentNR
Plastino et al,22
2010
Cohort1 year10476.2ADDSM-IVUse of antidiabetic medication or blood glucose >11Oral agents only, insulin plus oral agentsNR
Rhee et al,
2014
Cohort3.4 years1957NRNRNRNRHypoglycemic eventNR
Sato et al,
2011
RCT6 months4277.4NRNINCDS, CDR score 0.5 or 1DM drug Rx or elevated FBGPioglitazone in addition to use antidiabetic medicationsNo pioglitazone only regular antidiabetic medications
Trento et al,
2015
Cohort8 years49866.8NRNRNRInsulinNo insulin
Whitmer et al,25
2013
Cohort5 years14 891NRNRNRNRMetformin, sulfonylurea, thiazolidinedione, insulinSU acted as reference
Whitmer et al,40*
2009
Cohort3.8 years16 66766.3Dementia, AD, VaDICD-9Medical records, pharmacy RxOne, two, or three episodes of severe hypoglycemia requiring hospitalNR
Yaffee et al,*
2013
Cohort12 years78374.6NRICD-9Self-report, antidiabetic medication, elevated FBG according to ADA criteriaHypoglycemic eventNo hypoglycemic event
Yuan et al,
2015
Cohort2 yearsNRNRNRSelf-report, diagnosis codes in Medicare claims, dementia drug useNRMetformin, thiazolidinedione, insulinNR
Zullo et al,38
2017
CohortNR2016NRNR1-point increase in MDS Cognitive Performance Scale scoreNRDPP-4 inhibitorSU
  • 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.