The Cardiovascular,renal And Safety Outcomes Of Sodium-glucose Transporter 2 Inhibitors In Patients With Type 2 Diabetes Mellitus And Renal Insufficiency:A Systematic Review And Meta-analysis

Objective: It has been verified that sodium-glucose transporter-2(SGLT-2)inhibitors truly have cardiovascular protection and renoprotection in T2 DM,but the use of SGLT-2 inhibitors on T2 DM patients with kidney diseases has been limited by kidney function.Therefore,we conducted a systematic review and meta-analysis on T2 DM patients with renal insufficiency to evaluate the effects of SGLT2 inhibitors on cardiovascular and renal outcomes and the safety risks of their use,and provide more theoretical basis for their application in T2 DM patients with renal insufficiency.Methods: We conducted literature searches in Pub Med,EMBASE,Cochrane Library,Clinical Trials.gov,Chinese National Knowledge Infrastructure,Wanfang,and Chinese Biomedical Literature etc.All the English publications of randomized controlled trails in the treatment of T2 DM with renal insufficiency up to February 2021 have been searched.We Screened the RCTs that meet the inclusion criteria,evaluated the quality of the literature,extracted the data and used Revman5.4.1 and STATA16.0 for statistical analysis.For cardiovascular,renal and safety outcomes,we sought to use,in order of preference,hazard ratios and 95%confidence intervals or the risk ratio and 95% confidence intervals.Results: Data were obtained from 14 studies with a total of 30301 participants involved.In patients with T2 DM and renal insufficiency,SGLT2 inhibitors decrease the risk of the major adverse cardiovascular events[HR=0.81,95%CI(0.75,0.88)],cardiovascular death[HR=0.81,95%CI(0.73,0.91)],hospitalization for heart failure[HR=0.64,95%CI(0.54,0.75)],cardiovascular death/hospitalization for heart failure[HR=0.72,95%CI(0.63,0.81)],all-cause death [HR=0.80,95%CI(0.65,0.98)] and composite renal outcome[HR=0.66,95%CI(0.56,0.77)].There was no difference between the SGLT2 inhibitor group and the control group in fatal/nonfatal MI[HR=0.89,95%CI(0.76,1.05)],fatal/nonfatal stroke[HR=0.88,95%CI(0.72,1.08)].There was no evidence of additional risks of hypoglycaemia[RR=0.95,95%CI(0.88,1.02)],urinary tract infection[RR=1.05,95%CI(0.97,1.13)],acute kidney injury[0.83,95%CI(0.65,1.06)],bone fractures[RR=0.95,95%CI(0.80,1.13)],amputation[RR=1.08,95%CI(0.82,1.42)],hyperkalaemia[RR=0.75,95%CI(0.63,0.90)] and hypertension[RR=0.65,95%CI(0.53,0.78)] with SGLT2 inhibition in T2 DM and renal insufficiency.But SGLT2 inhibitors increase the risk of the genital infection[RR=2.83,95%CI(2.23,3.59)],volume depletion[ RR=1.22,95%CI(1.08,1.39)] and diabetic ketoacidosis [RR=2.60,95%CI(1.49,4.56)].Conclusions: Recently obtainable data shows that,in patients with T2 DM and renal insufficiency,SGLT2 inhibitors decrease the risk of cardiovascular and renal outcomes,without increasing the risk of hypoglycemia,urinary tract infection,acute kidney injury,fractures,amputations,hyperkalemia,and hypertension.However,SGLT2 inhibitors increased the risk of genital infection,hypovolemia,and diabetic ketoacidosis in people with T2 DM combined with renal insufficiency.Therefore,it is necessary to further explore the appropriate drug dosage.