Clinical Efficacy And Safety Study Of SGLT-2 Inhibitor Dapagliflozin To Improve Cognitive Dysfunction In Combination With Type 2 Diabetes

Objective To investigate the effects of Dapagliflozin on cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus and its related factors.Methods This was a retrospective study.A total of 200 patients who were hospitalized in the Department of Endocrinology,the Second Affiliated Hospital of Anhui Medical University from August 2021 to August 2022 were recruited.100 of them in the Dapagliflozin group（Use of Dapagliflozin combined with other hypoglycemic agents,and glucagon-like peptide-1 receptor agonists were excepted）.100 were controls（sodium-glucose cotransporter 2 receptor inhibitors and glucagon-like peptide-1 receptor agonists were excepted）.Clinical data of this hospitalization and fasting blood glucose as well as glycosylated hemoglobin changes from 12 months before admission to the present were collected.Long-term glycemic variability was calculated.plasma Abeta40 and Abeta42、TNF-a、IL-6 were detected.The t-test,χ2test,and Mann-Whitney U test were used to analyze the differences between groups,and multiple logistic regression was used to analyze the influencing factors associated with cognitive dysfunction.Results（1）There was no difference in age,sex,diabetes duration,education duration,SBP,DBP,BMI,BSA,Hb A_1c,FPG,FC-P,TNF-a,IL-6,Isletβfunction,ALT,AST,TSH,Hb A_lc-M,FPG-M between the Dapagliflozin and control group（P>0.05）.Compared with the control group,MMSE score,MOCA score,e GFR,and plasma Aβ40 level were significantly higher in the Dapagliflozin group（P<0.05）;meanwhile,MCI prevalence assessed by MMSE and MOCA,insulin resistance（IR）,TC,TG,UACR,plasma Aβ42 level,Aβ42/Aβ40 ratio,Hb A_lc-SD,Hb A_lc-CV,FPG-SD,and FPG-CV were significantly lower with statistically significant differences（P<0.05）.（2）Patients in the Dapagliflozin group were divided into MCI and non-MCI subgroups based on Mo CA scores.There was no difference in sex,diabetes duration,education duration,DBP,BMI,BSA,Hb A_1c,FPG,plasma TNF-αand IL-6,plasma Aβ40 and Aβ42 level,TC,TG,ALT,AST,e GFR,UACR,TSH,Hb A_lc-M,Hb A_lc-CV,FPG-CV,Isletβfunction between the MCI and non-MCI subgroup（P>0.05）.Compared with the MCI subgroup,duration of Dapagliflozin treatment,MMSE and MOCA Scores in the non-MCI group were significantly increased（P<0.05）;There were statistically significant decreased in the non-MCI group in age,SBP,IR,FC-P,Hb A_lc-SD,FPG-M,FPG-SD（all P<0.05）.Multiple logistic regression analysis showed that duration of Dapagliflozin treatment was a protective factor for cognitive dysfunction（OR=0.473,95%CI:0.308～0.725,P=0.001）;age,insulin resistance,Hb A_lc-SD were risk factors（OR=1.118,95%CI:1.05～1.190,P=0.001;OR=1.850,95%CI:1.017～3.365,P=0.044;OR=4.325,95%CI:1.186～15.776,P=0.027）。Conclusions Dapagliflozin may improve cognitive function and significantly reduce the incidence of mild cognitive impairment（MCI）in middle-aged and elderly patients with T2DM,which may be related to its reduced degree of insulin resistance and blood glucose variability.