The effects of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists on cognitive functions in
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REVIEW ARTICLE
The effects of dipeptidyl peptidase‑4 inhibitors and glucagon‑like peptide 1 receptor agonists on cognitive functions in adults with type 2 diabetes mellitus: a systematic review and meta‑analysis Yuxin Jin1,2 · Hang Zhao2 · Yilin Hou1,2 · Guangyao Song1,2 Received: 2 February 2020 / Accepted: 27 March 2020 © Springer-Verlag Italia S.r.l., part of Springer Nature 2020
Abstract Aims The effects of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors/DPP-4I) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) on cognition in patients with type 2 diabetes mellitus (T2DM) remain controversial. We aimed to explore this clinical issue through a systematic review and meta-analysis. Methods PubMed, EMBASE and the Cochrane Library were searched, and data were expressed as mean difference (MD) or hazard ratio (HR)/odds ratio (OR) with a 95% confidence interval (CI). Heterogeneity was assessed using the Chi-squared test and the I2 statistic. The study was registered with PROSPERO (ID: CRD42019138777). Results Eleven studies (n = 304,258 T2DM patients) were included in our review. In the DPP-4I group, six studies were enrolled to estimate ΔMini-Mental State Examination (MMSE) scores from baseline to the final evaluations after DPP-4I treatment, which showed no statistical difference (MD 0.20; 95% CI − 0.75 to 1.15, p = 0.68). ΔMMSE scores in the DPP-4I group and the other antidiabetic groups were compared, revealing no statistical difference (MD 0.57; 95% CI − 0.05 to 1.19, p = 0.07). Two cohort studies were pooled to determine the HRs for dementia, showing a lower risk of dementia after DPP4I treatment (HR 0.52; 95% CI 0.29–0.93, p = 0.03). In the GLP-1 analogs group, two studies were included, one of which revealed a downward trend in the risk of dementia after GLP-1 analog treatment, while the other revealed no significant difference after incretins treatment. Conclusions Currently there is not enough irrefutable evidence to support the hypothesis of positive effects of incretins on cognition. Further clinical studies need to be performed. Keywords Type 2 diabetes mellitus · Dipeptidyl peptidase-4 inhibitors · Glucagon-like peptide 1 receptor agonists · Cognition · Meta-analysis
Introduction
Managed by Massimo Federici. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00592-020-01529-1) contains supplementary material, which is available to authorized users.
In the last 20 years, a close correlation between type 2 diabetes mellitus (T2DM) and cognitive impairment has been shown by epidemiological, clinical and basic experimental data [1–4]. Hyperinsulinemia and insulin resistance, which are major pathophysiological features of T2DM, have
* Guangyao Song [email protected]
1
Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei, People’s Republic of China
Yuxin Jin [email protected]
2
Endocrinology Department, Hebei General Hospital, Shijiazhuang 050051, Hebei, People’s Republic of China
Hang
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