| Objective:To systematically evaluate the cardio-renal outcome and prognosis of metformin on type 2 diabetes mellitus patients with chronic kidney disease(CKD)or chronic heart failure(CHF)by Meta-analysis.Methods:We searched databases including Pub Med,Cochrane Library,Embase,Web of Science,Sino Med,CNKI,Wan Fang data and VIP Journal to collect published randomized controlled trials(RCT)and observational cohort studies about metformin therapy in T2 DM patients with chronic kidney disease or chronic heart failure from January 2003 to January 2023.According to the inclusion and exclusion criteria,relevant literatures were screened out,then extracted data after quality assessment according to Jadad scale which is used to evaluate controlled trials and NOS scale for observational cohort studies.We employed Rev Man5.4 statistical software to analyze the data,performed sensitivity analysis to evaluate the stability of the research results,and drew funnel plot to assess publication bias.Result:A total of 21 eligible original studies were enrolled in our study,including one study involving 4010 T2 DM patients with CKD and CHF,6 studies about T2 DM with CKD involving 74417 patients and 14 studies with chronic heart failure CHF involving 18551 patients.The Meta-analysis results:(1)Meta-analysis results of T2 DM subjects with CKD: In terms of outcome,metformin group led to a significant drop in risk of all-cause mortality(RR=0.67,95%CI[0.54,0.84],P=0.0005])compared with non-metformin group.No statistically significant differences were found in reducing incidences of MACE(RR=0.91,95%CI [0.78,1.08],P=0.28),non-fatal myocardial-infarction(RR=0.82,95%CI[0.64,1.05],P=0.11),non-fatal stroke(RR=1.07,95%CI[0.72,1.58],P=0.75)between two groups.But metformin group had a significant decline in risk of cardiovascular mortality(CVM;RR=0.73,95%CI[0.59,0.90],P=0.003).A statistically significant difference was found in reducing incidence of end stage renal diseases(ESRD;RR=0.83,95%CI[0.78,0.88],P<0.00001]),metformin group had significant low risk of progression to ESRD than the non-metformin group.In metabolic acidosis(MA;RR=0.91,95%CI[0.51,1.64],P=0.77),there was no significant difference between two groups.(2)Meta-analysis results of T2 DM subjects with CHF: In outcome,compared to the non-metformin group metformin group had significant drop in risk of all-cause mortality(RR=0.72,95%CI[0.60,0.87],P=0.0004]).When control group was divided into SU subgroup and non-SU subgroup according to different drug exposure,and subgroup analysis results showed that compared to the SU subgroup(RR=0.71,95%CI [0.45,1.13],P=0.15])there was no significant difference between two groups.But metformin group had significant low risk of all-cause death compared to non-SU subgroup(RR=0.72,95%CI[0.59,0.89],P=0.002]).There was no significant difference in heart failure hospitalization(RR=0.85,95%CI [0.70,1.04],P=0.12])between two groups.Metformin group had a significant decrease in risk of cardiovascular mortality(CVM;(RR=0.52,95%CI [0.29,0.92],P=0.03])than non-metformin group.In cardiac function,the difference were statistically significant in improving Left ventricular ejection fractions(LVEF;WMD=1.47,95%CI[-1.79,4.72],P=0.38),left ventricular end diastolic dimension(LVEDD;WMD=-2.79,95%CI[-6.56,0.98],P=0.15)between two groups,metformin group had a significant advantage in improving N-terminal pro-B-type natriuretic peptide(NT-pro BNP;WMD=-132.91,95%CI[-173.03,-92.79],P<0.00001)compared with non-metfromin group.Conclusion:1.In type 2 diabetes patients with chronic kidney diseases,metformin is associated with reduced risk of all-cause death and cardiovascular death,and it can delay progression to end stage renal diseases in patients with chronic kidney disease without increasing the risk of metabolic acidosis,so it is relatively safe and beneficial.2.In type 2 diabetes patients with chronic kidney diseases,metformin is associated with reduced risk of all-cause death and cardiovascular death,and it can delay progression to end stage renal diseases in patients with chronic kidney disease without increasing the risk of metabolic acidosis,so it is relatively safe and beneficial. |
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