Cognitive-improving Effects Of Novel Hypoglycemic Drugs GLP-1 Receptor Agonists ——A Meta-Analysis Based On Randomized Controlled Trials

Objective: To explore cognitive-improving effects of novel hypoglycemic drugs GLP-1 receptor agonists on cognitive impairment patients with or without diabetes mellitus and its impact on risk factors associated with cognitive decline.Methods: Using subject words combined with free words to search multiple English and Chinese databases and screen randomized controlled trials（RCT）related to this Meta analysis.The retrieval time was from the establishment of the database to December 28,2021.The Chinese and English literatures that met the inclusion criteria were selected,and the quality assessment and data extraction were performed on the included literatures.The Review manager 5.4.1 software was used to merge and analyze the data of the outcome indicators,and the subgroup analysis of the outcome indicators with greater heterogeneity was performed to find the possible sources of heterogeneity.Sensitivity analysis of outcomes with greater heterogeneity was performed using Stata16.0 to further identify suspected sources of heterogeneity.Whether there is publication bias in the research results was qualitatively judged by making a funnel plot,and quantitative analysis was carried out using Begg and Egger tests.Results: A total of 17 RCTs were included,including 10,092 patients with cognitive impairment,5,091 in the intervention group and 5,001 in the control group.Meta-analysis showed that the MMSE score（[SMD=1.09,95%CI（0.57,1.61）,P<0.05]）,Mo CA score（[SMD=1.29,95%CI（0.67,1.90）,P<0.05]）of patients with cognitive impairment in the GLP-1 RA intervention group,which were higher than those in the control group;the incidence of hypoglycemia（[RR=0.35,95%CI（0.23,0.53）,P<0.05]）,fasting blood glucose（[MD=-0.54,95%CI（-0.90,-0.19）,P<0.05]）,2h postprandial blood glucose（[SMD=-0.72,95%CI（-1.24,-0.21）,P < 0.05]）,glycosylated hemoglobin（[SMD=-1.09,95%CI（-1.66,-0.52）,P < 0.05]）,total cholesterol（[SMD=-0.58,95%CI（-0.92,-0.25）,P < 0.05]）,The body mass index([MD=-0.89,95%CI（-1.53,-0.25,P<0.05]）was lower than that of the control group,and the above results were significantly different.The incidence of gastrointestinal adverse reactions in the intervention group（[RR=1.35,95%CI（0.75,2.41）,P>0.05]）was higher than the control group,but the difference was not statistically significant.Conclusion: GLP-1 receptor agonists have a certain cognitive improvement effect on cognitive impairment patients with or without diabetes,and have a certain positive regulation on the risk factors of cognitive decline,such as hyperglycemia,hypoglycemia,hyperlipidemia and obesity.The Meta-analysis has certain limitations,and more large,multi-center RCTs are needed to further validate the findings.