| Objectives To investigate the effect of the third drug addition(Ins or DPP-4i)on risk of adverse events in type 2 diabetes mellitus(T2DM)patients,who failed to be treated with Met+Aca,providing the selection of therapeutic drugs for T2DM in clinic.Methods In a retrospective cohort study,patients diagnosed with T2DM were divided into the Met+Aca+DPP-4i or Met+Aca+Ins two groups with Telephone follow-up in Shijiazhuang Second Hospital during November 2017 to August 2020.The follow-up wasn’t terminated until a preset outcome occurred,which was recorded.There were four preset outcomes including non-fatal cardiovascular diseases,all-cause death,severe hypoglycemia,and comprehensive event(all-cause death,non-fatal cardiovascular events,and severe hypoglycemia).After propensity score matching(PSM,1:1 matching information,the setting of callipers calibration was 0.02),the risk of comprehensive events after the third drug treatment in T2DM patients was analyzed by Cox proportional risk model.Subgroup analysis was performed on the covariates affecting the risk of comprehensive events.Results A total number of enrolled T2DM patients was 1570 finally,including 1089patients treated with Met+Aca+Ins and 481 patients treated by Met+Aca+DPP-4i,followed434 cases in both groups after 1:1 PSM.Compared with the Met+Aca+Ins group,the incidences of comprehensive events(6.53/100 person-per year),non-fatal cardiovascular disease(5.03/100 person-years),all-cause death(0.73/100 person year),and severe hypoglycemic(0.73/100 person-years)were lower in the Met+Aca+DPP-4i group.The results of multivariate analysis by Cox proportional hazard model on the risk of comprehensive events was 67%in Met+Aca+DPP-4i group lower than that in Met+Aca+Ins group[HR=0.34,95%CI(0.23～0.50),P<0.001].Compared with the Met+Aca+Ins group,the risk of non-fatal cardiovascular disease was 52%lower[HR=0.48,95%CI(0.30～0.77),P=0.002],and the risk of all-cause death was 81%lower[HR=0.19,95%CI(0.07～0.56),P=0.003],The risk of severe hypoglycemic events was reduced by80%[HR=0.20,95%CI(0.07～0.59),P=0.003]in the Met+Aca+Ins group.The result of log-rank test showed that the survival rate of patients in Met+Aca+DPP-4i group was higher than that in Met+Aca+Ins group(χ~2=32.849,P<0.001).The results of the covariate interaction analysis showed that,In patients with endogenic creatinine clearance>120ml/min,no other CHD,adequate sleep(>7 h/d),non-smoking,and no family history of cardiovascular disease,Met+Aca+DPP-4i treatment was more significant in reducing the risk of comprehensive events than Met+Aca+Ins treatment for T2DM patients(P-values were 0.018,0.013,0.035,0.031,0.042,respectively);In patients with total cholesterol<5.2mmol/L,low-density lipoprotein 3.59 mmol/L,endogenic creatinine clearance of 120ml/min,and no family history of cardiovascular disease,Met+Aca+DPP-4i treatment wasmore significant in reducing the risk of Met+Aca+Ins(P values 0.043,0.049,0.018,0.014,respectively).Conclusions In T2DM patients who failed Met and Aca,addition of DPP-4i significantly reduced the risk of comprehensive events,composite non-fatal cardiovascular events,all-cause death and severe hypoglycemic events compared with added Ins,with longer overall and better T2DM patients receiving Met+Aca+DPP-4i group compared to Met+Aca+Ins group.More effective in reducing the risk of composite events in patients with endogenic creatinine clearance>120 ml/min,no other CHD,adequate sleep,nonsmoking and T2DM,and in reducing complex nonfatal cardiovascular events in T2DM patients with total cholesterol<5.2 mmol/L,LDL 3.59 mmol/L,endogenous creatinine clearance 120 ml/min,and no family history of cardiovascular disease.Figure 14;Table 12;Reference 168... |
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