. 2018 Nov 16;6(1):e000563. doi: 10.1136/bmjdrc-2018-000563

Table 1*.

Characteristics of included studies

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.