The Renal Protective Effect And Safety Of SGLT2 Inhibitors On Diabetic Nephropathy: A Systematic Review And Meta-analysis

Objective: To systematically evaluate the nephroprotective effect and safety of sodium-glucose cotransporter 2(SGLT2)inhibitors in patients with diabetic nephropathy(DN).Methods: the biomedical databases such as foreign PubMed,EmbaseTheCochraneLibrary and domestic China knowledge Network(CNKI)and Wanfang database were searched by computer.The time for literature retrieval ends in December 2019.To collect all kinds of published English randomized controlled trials about the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in the treatment of diabetic nephropathy,evaluated the quality of the literature that met the inclusion criteria and extracted the data,and then cross-checked.After screening,statistical software RevMan 5.3 was used to evaluate and analyze the data of the literature that met the inclusion criteria.Results: A total of 9 randomized controlled trials were included in the analysis,including 28349 patients.Meta analysis showed that in terms of renal protective effect: For patients with diabetic nephropathy,Estimation of glomerular filtration rate(eGFR)showed a downward trend during the short-term course of SGLT2 inhibitors(26 weeks)[P=0.01,WMD=1.77,95%CI(0.40,3.14)],With the gradual prolongation of the course of treatment,the decreasing trend of eGFR slowed down at 52 weeks,and showed protective effect compared with the control group[P=0.004,WMD=-2.10,95%CI(-3.54,-0.66)].The use of SGLT2 inhibitors can reduce the Urinary micro albuminuria creatinine ratio(UACR)and reduce albuminuria to protect renal function [P<0.00001,WMD=-107.75,95%CI(-146.80,-68.71)].Safety analysis: the total incidence of adverse events in patients treated with SGLT2 inhibitors decreased,[RR=0.94,95%CI(0.92,0.96),p<0.00001],but it could increase the reproductive tract infection rate [RR=2.24,95%CI(1.19,4.24),p=0.01],and also increased the incidence of adverse events related to volume reduction [RR=1.97,95%CI(1.45,2.69),p<0.0001],and increased the incidence of adverse events related to volume reduction.The incidence of hypoglycemia events[RR=0.72,95%CI(0.49,1.07),p=0.11] and urinary tract infection rate [RR=1.16,95%CI(0.90,1.50),p=0.25]of hypoglycemia events were not significantly different from those of the control group.Conclusion: The application of SGLT2 inhibitors can reduce the eGFR,of patients in a short time.Based on its mechanism of action,it should not be regarded as an adverse reaction,but a manifestation of curative effect.With the extension of the course of treatment,the decrease of eGFR slows down and albuminuria decreases significantly,showing a protective effect on the kidney.SGLT2 inhibitors generally reduced the incidence of adverse events,blood glucose safety was good,did not increase urinary tract infection rate,but reproductive tract infection rate and volume reduction related adverse events increased.At present,there is a lack of sufficient data for CKD4 and CKD5 in randomized controlled trials,so it is not recommended for the time being.Due to the limitations of this study,the conclusions of this meta analysis need to be treated seriously and cautiously.We look forward to more studies and experiments specifically targeting SGLT2 inhibitors in patients with diabetic nephropathy and chronic renal insufficiency(CKD).