| Background:Cardiovascular disease and its complications are currently one of the most important causes of death in patients with diabetes.Diabetes patients are more than 10 times more likely to suffer from cardiovascular disease in their lifetime than ordinary people,which brings an increasingly heavy economic burden to patients and the national health care system.Most patients with type 2 diabetes(T2DM)are associated with cardiovascular disease risk factors,such as obesity,hypertension,hyperlipidemia,and high uric acid.Before 2018,many national and international organizations such as the American Diabetes Association(ADA)and the European Diabetes Research Association(EASD)adopted metformin as the first choice for the treatment of T2 DM.If T2 DM patients are associated with cardiovascular disease risk factors,can drugs that reduce major cardiovascular adverse events and/or cardiovascular mortality be the first choice.Sodium-dependent glucose transporters 2(SGLT-2)inhibitors are new oral hypoglycemic drugs that have come out in recent years and have obvious protective effects on diabetes combined with cardiovascular disease.However,the mechanism of SGLT-2 inhibitors for cardiovascular protection is still unclear.Recent studies have also found that disturbances in the structure and function of intestinal flora are some of the important risk factors for cardiovascular disease in T2 DM patients.Therefore,this study plan is to adopt a parallel randomized controlled clinical trial method to observe the clinical efficacy of the SGLT-2 inhibitor empagliflozin in the treatment of patients with new-onset T2 DM with cardiovascular disease risk factors,and through 16 s RNA,metabolomics and other techniques to explore the mechanism of intestinal flora changes.Objective:1.To evaluate the clinical efficacy and safety of empagliflozin as the first choice for the treatment of patients with new-onset T2 DM with cardiovascular disease risk factors.2.To explore the mechanism of changes in intestinal microflora structure or function involved in the occurrence,development,and outcome of cardiovascular disease when empagliflozin is used to treat patients with new-onset T2 DM with cardiovascular disease risk factors.Methods:1.This trial is a parallel randomized controlled trial.A total of 116 volunteers were recruited,of which76 were eligible for clinical research.Randomly divided into the empagliflozin group(experimental group,group E)and metformin group(control group,group M)in the order of random number generation table.2.The trial period was 12 weeks.Group E was treated with empagliflozin and group M was treated with metformin.Both groups of volunteers were given routine dietary education according to the "Guidelines for the Prevention and Treatment of Type 2 Diabetes" before enrollment.3.Hemoglobin A1c(Hb A1c),oral glucose tolerance test(OGTT),insulin release test,body weight,body mass index(BMI),waist circumference,Waist-hip ratio(WHR),Fat mass percentage(FM%),Systolic blood pressure(SBP),Dbdiastolic blood pressure(DBP),Cholesterol total(TC),triglyceride(TG),low-density lipoprotein(LDL-C),high-density lipoprotein(HDL-C),urine microprotein/creatinine value(Urinary albumin/creatinine ratio(A/C)),Uric acid(UA),Alanine aminotransferase(ALT),Aspartate aminotransferase(AST),Serum creatinine(Serum creatinine,Scr),etc were measured before and 12 weeks after the intervention.Adverse events were strictly recorded.And the changes before and after the intervention and the differences between the two groups were compared.4.Statistical analysis of data was performed using SPASS 22.0.Results:1.General information of the volunteers: A total of 69 patients with T2 DM and atherosclerotic cardiovascular disease risk factors completed follow-up,of which 37 were in the englitazone group and 32 were in the metformin group.Before the intervention,age,gender,H1 b Ac,fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG),HOMA-?,weight,BMI,waist circumference,WHR,Systemic FM%,SBP,DBP,TC,TG,LDL-C,HDL-C,A/C,UA,creatinine clearance(Epidermal growth factor receptor,e GFR),ALT,AST showed no statistical difference(P> 0.05)2.Glucose metabolism indicators:(1)Hb A1 c in the empagliflozin group and metformin group were significantly lower than before intervention(P <0.05);there was no statistical difference in the decrease in Hb A1 c between the two groups(P> 0.05).The number of people who met the standard was 49,and the total compliance rate was 71%.Among them,25 people met the standard of Hb A1 c in the empagliflozin group,and the rate of compliance was 65%,there was no significant difference in compliance rate betweenthe two groups(P > 0.05).(2)FBG in both groups showed a downward trend compared with before intervention;there was no statistical difference in the degree of FBG decline between the two groups after an intervention(P> 0.05).(3)PBG in both groups was significantly lower than before the intervention.The decrease in PBG in the empagliflozin group was better than that in the metformin group(P> 0.05).(4)HOMA-IR in both groups was significantly lower than before intervention(P <0.05).3.Indicators of risk factors for atherosclerotic cardiovascular disease:(1)Body weight,BMI,waist circumference,WHR,and whole-body FM% in both the empagliflozin group and the metformin group decreased significantly before the intervention(P<0.05).Comparison between the two groups,weight loss in the empagliflozin group was more significant than that in the metformin group(P<0.05).(2)SBP and DBP decreased significantly in the empagliflozin group(P <0.05),and there was no statistically significant decrease in the metformin group(P>0.05),while the decrease in SBP and DBP in the empagliflozin group was significantly lower than that in the metformin group(P <0.05).(3)the TG level in the empagliflozin group was significantly lower than that before intervention(P < 0.05),and there was no significant change in TC and LDL-C before intervention(P > 0.05).The TC level in the metformin group was significantly lower than that before intervention(P < 0.05),and there was no significant change in TG,LDL-C,and HDL-C before intervention(P > 0.05).There was no statistical significance in the decrease of TC,TG,LDL-C,and HDL-C between the two groups(P>0.05).(4)There was no significant change in urine A/C in the two groups compared with that before the intervention(P > 0.05).(5)UA was significantly lower in the ungulate group than before the intervention(P < 0.05).There was no significant change in metformin group compared with that before the intervention(P > 0.05): the degree of decline was significantly higher in the empagliflozin group than that in the metformin group(P<0.05).4.Indicators related to gut microbiota: The empagliflozin group showed significant changes in intestinal microflora at the 4th week of the intervention,and continued to change.At the 12 th week,there was still a significant difference from before the intervention.The metformin group began to show significant changes in intestinal flora at the 8th week of intervention,but at the 12 th week,it started to recover to the baseline level.The gut microbiota of butyric acid and acetic acid produced in the empagliflozin group increased at the 12 th week compared with the previous group.5.Safety indicators: ALT in the empagliflozin group decreased compared with before intervention(P< 0.05),ALT in the metformin group showed no significant change compared with before intervention(P >0.05),and AST and e GFR levels in both groups showed no significant change compared with before intervention(P > 0.05).Conclusion:1.Empagliflozin can significantly improve the glucose metabolism function and cardiovascular disease risk factors of patients with new-onset T2 DM with cardiovascular disease risk factors,and can be used as the first choice for the treatment of patients with new-onset T2 DM with cardiovascular disease risk factors.2.Empagliflozin can increase the abundance of bacteria producing short-chain fatty acids such as butyric acid and acetic acid,reduce systemic inflammatory response,and improve atherosclerosis,which may be one of the mechanisms of its cardiovascular protection for T2 DM. |
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