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Cardiovascular and Metabolic Risk
Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis
  1. Jacqueline M McMillan1,2,
  2. Bria S Mele2,
  3. David B Hogan1,
  4. Alexander A Leung1,2
  1. 1 Department of Medicine, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
  2. 2 Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
  1. Correspondence to Jacqueline M McMillan; mcmilljm{at}ucalgary.ca

Abstract

Background The association between diabetes mellitus (DM) treatment and dementia is not well understood.

Objective To investigate the association between treatment of diabetes, hypoglycemia, and dementia risk.

Research design and methods We performed a systematic review and meta-analysis of pharmacological treatment of diabetes and incident or progressive cognitive impairment. We searched Ovid MEDLINE, Embase, Cochrane Central Registry of Controlled Trials, and PsychINFO from inception to 18 October 2017. We included cross-sectional, case–control, cohort, and randomized controlled studies. The study was registered with PROSPERO (ID CRD42017077953).

Results We included 37 studies into our systematic review and 13 into our meta-analysis. Ten studies investigated any antidiabetic treatment compared with no treatment or as add-on therapy to prior care. Treatment with an antidiabetic agent, in general, was not associated with incident dementia (risk ratio (RR) 1.01; 95% CI 0.93 to 1.10). However, we found differential effects across drug classes, with a signal of harm associated with insulin therapy (RR 1.21; 95% CI 1.06 to 1.39), but potentially protective effects with thiazolidinedione exposure (RR 0.71; 95% CI 0.55 to 0.93). Severe hypoglycemic episodes were associated with a nearly twofold increased likelihood of incident dementia (RR 1.77; 95% CI 1.35 to 2.33). Most studies did not account for DM duration or severity.

Conclusions and limitations The association between treatment for diabetes and dementia is differential according to drug class, which is potentially mediated by hypoglycemic risk. Not accounting for DM duration and/or severity is a major limitation in the available evidence base.

  • diabetes mellitus
  • treatment
  • dementia
  • mild cognitive impairment

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjdrc-2018-000563

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    Footnotes

    • Contributors JMM: literature search, study design, data collection, data analysis and interpretation, and writing. BSM: literature search, study design, data collection, data analysis and interpretation, and writing. DBH: study design, data analysis and interpretation, and writing. AAL: study design, data analysis and interpretation, and writing.

    • Funding The Brenda Strafford Foundation Chair in Geriatric Medicine has provided funding for Open Access Publication. JMM has received an academic scholarship for tuition for Graduate Studies. BSM has received an academic scholarship from the Government of Alberta. AAL is a recipient of the Hypertension Canada New Investigator Award.

    • Disclaimer The funding sources had no role in the study design or decision to submit the manuscript for publication.

    • Competing interests None declared.

    • Patient consent Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No additional data are available.