Dataset Information

Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: Pooled analysis from 5 cohorts.

ABSTRACT: OBJECTIVE:To determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties. RESEARCH DESIGN AND METHODS:Findings were pooled from 5 population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differences between users and non-users of insulin, metformin and sulfonylurea were assessed in each cohort for cognitive and brain MRI measures using linear regression models, and cognitive decline and dementia/AD risk using mixed effect models and Cox regression analyses, respectively. Findings were then pooled using meta-analytic techniques, including 3,590 individuals with diabetes for the prospective analysis. RESULTS:After adjusting for potential confounders including indices of glycemic control, insulin use was associated with increased risk of new-onset dementia (pooled HR (95% CI) = 1.58 (1.18, 2.12);p = 0.002) and with a greater decline in global cognitive function (β = -0.014±0.007;p = 0.045). The associations with incident dementia remained similar after further adjustment for renal function and excluding persons with diabetes whose treatment was life-style change only. Insulin use was not related to cognitive function nor to brain MRI measures. No significant associations were found between metformin or sulfonylurea use and outcomes of brain function and structure. There was no evidence of significant between-study heterogeneity. CONCLUSIONS:Despite its advantages in controlling glycemic dysregulation and preventing complications, insulin treatment may be associated with increased adverse cognitive outcomes possibly due to a greater risk of hypoglycemia.

SUBMITTER: Weinstein G

PROVIDER: S-EPMC6377188 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: Pooled analysis from 5 cohorts.

Weinstein Galit G Davis-Plourde Kendra L KL Conner Sarah S Himali Jayandra J JJ Beiser Alexa S AS Lee Anne A Rawlings Andreea M AM Sedaghat Sanaz S Ding Jie J Moshier Erin E van Duijn Cornelia M CM Beeri Michal S MS Selvin Elizabeth E Ikram M Arfan MA Launer Lenore J LJ Haan Mary N MN Seshadri Sudha S

PloS one 20190215 2

<h4>Objective</h4>To determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties.<h4>Research design and methods</h4>Findings were pooled from 5 population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differenc ...[more]

PMID: 30768625

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Project description:ImportanceBefore 2016, safety concerns limited metformin use in patients with kidney disease; however, the effectiveness of metformin on clinical outcomes in patients with reduced kidney function remains unknown.ObjectiveTo compare major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function who continued treatment with metformin or a sulfonylurea.Design, setting, and participantsRetrospective cohort study of US veterans receiving care within the national Veterans Health Administration, with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. There were 174 882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold (estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine ≥1.4 mg/dL for women or ≥1.5 mg/dL for men). Patients were followed up from reduced kidney function threshold until MACE, treatment change, loss to follow-up, death, or study end (December 2016).ExposuresNew users of metformin or sulfonylurea monotherapy who continued treatment with their glucose-lowering medication after reaching reduced kidney function.Main outcomes and measuresMACE included hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. The analyses used propensity score weighting to compare the cause-specific hazard of MACE between treatments and estimate cumulative risk accounting for the competing risks of changing therapy or noncardiovascular death.ResultsThere were 67 749 metformin and 28 976 sulfonylurea persistent monotherapy users; the weighted cohort included 24 679 metformin and 24 799 sulfonylurea users (median age, 70 years [interquartile range {IQR}, 62.8-77.8]; 48 497 men [98%]; and 40 476 white individuals [82%], with median estimated glomerular filtration rate of 55.8 mL/min/1.73 m2 [IQR, 51.6-58.2] and hemoglobin A1c level of 6.6% [IQR, 6.1%-7.2%] at cohort entry). During follow-up (median, 1.0 year for metformin vs 1.2 years for sulfonylurea), there were 1048 MACE outcomes (23.0 per 1000 person-years) among metformin users and 1394 events (29.2 per 1000 person-years) among sulfonylurea users. The cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% CI, 0.75-0.86) compared with sulfonylureas, yielding an adjusted rate difference of 5.8 (95% CI, 4.1-7.3) fewer events per 1000 person-years of metformin use compared with sulfonylurea use.Conclusions and relevanceAmong patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE.

Dataset Information

Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: Pooled analysis from 5 cohorts.

Publications

Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: Pooled analysis from 5 cohorts.

Similar Datasets

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