The Effect Of Metformin On The Prognosis Of Patients With Heart Failure With Preserved Ejection Fraction And Type 2 Diabetes Mellitus

Objective:Metformin is the first-line antidiabetic medication for type 2 diabetes mellitus(T2DM)and has cardiovascular protection.Some studies have suggested that metformin can improve the prognosis of patients with heart failure combined with T2DM.However,whether metformin has a protective effect on patients with heart failure with preserved ejection fraction(HFpEF)combined with T2DM is still unknow.This study aimed to explore the effect of metformin on patients with HFpEF combined with T2DM.Methods:This study collected clinical data of patients with HFpEF and T2DM who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Zhejiang University School of Medicine from January 1,2013 to December 31,2016,excluding the patients with acute heart failure,moderate or severe renal insufficiency,loss of follow-up,and not taking metformin continuously.Baseline parameters were balanced for metformin and nonmetformin users using the propensity score matching strategy.Kaplan-Meier analysis was used to compare the survival rates of HFpEF combined with T2DM in hospitalized patients with metformin treatment and nonmetformin treatment,and the independent risk factors affecting survival were explored through the multivariate Cox regression model.Results:A total of 276 patients with HFpEF combined with T2DM were included.Seventy nine patients were in the metformin group and 197 patients were in the non-metformin group,with a median follow-up of 48(34,60)months.The 1-year,2-year,3-year and 4-year survival rates of the metformin group were 100%,97.4%,92.1% and 92.1%,respectively,and the non-metformin group were 97.5%,93.4%,84.4% and 75.8%,with statistically significant differences(P=0.010).Cox regression model results showed that male(HR=1.813,95%CI: 1.006-3.267,P=0.048),hemoglobin level(HR=0.976,95%CI:0.960-0.992,P=0.003),and combined use of sulfonylureas(HR=0.439,95%CI: 0.202-0.955,P=0.038)were independent predictors of all-cause mortality risk.A total of 156cases(78 cases in each group)were included after the 1:1 propensity score matched.The 1-year,2-year,3-year and 4-year survival rates of the metformin group were 100%,97.4%,92.0% and 92.0%,respectively,and the non-metformin group were 97.4%,94.9%,84.2% and 76.0%,with statistically significance(P=0.031).Multivariate Cox regression analysis suggested that hemoglobin level(HR = 0.964,95%CI: 0.943-0.986,P=0.001)was an independent predictor of all-cause mortality risk.Meanwhile,combined use of metformin(HR=0.492,95%CI: 0.187-1.291,P=0.150)had a tendency to reduce all-cause mortality risk.Before and after the match,metformin did not improve cardiovascular mortality,all-cause hospitalization,or cardiovascular hospitalization.Conclusions:Among HFpEF patients with T2DM,patients in the metformin group had a tendency to improve survival(without statistically significance),as compared with those who did not take metformin.Meanwhile,the use of metformin did not improve cardiovascular mortality,all-cause hospitalization,or cardiovascular hospitalization.Hemoglobin levels was an independent predictor of all-cause mortality risk in HFpEF patients with T2DM.Prospective,large sample studies are necessary to determine the best treatment for HFpEF with type 2 diabetes.