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

Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis

Jacqueline M McMillan  1   2 , Bria S Mele  2 , David B Hogan  1 , Alexander A Leung  1   2
Affiliations

Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis

Jacqueline M McMillan et al. BMJ Open Diabetes Res Care. .

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.

Keywords: dementia; diabetes mellitus; mild cognitive impairment; treatment.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Relative risk of developing dementia with intensive versus non-intensive antidiabetic treatment. RR, risk ratio; TZD, thiazolidinedione.
Figure 2
Figure 2
Relative risk of developing dementia by treatment type. RR, risk ratio; TZD, thiazolidinedione.
Figure 3
Figure 3
Relative risk of developing dementia based on to the occurrence of one or more hypoglycemic events. RR, risk ratio.
See this image and copyright information in PMC

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