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

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 theI(2)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 Delta Mini-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). Delta MMSE 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 DPP-4I 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.