Systematic review and meta-analysis of Statins-Fibrates therapy in diabetic dyslipidemia patients

AIM： To evaluate the effcacy, effect of preventing cardio-vascular diseases and safety of statins-fbrates combination therapy in diabetic dyslipidemia patients.METHODS： We searched the databases of MEDLINE, EM-BASE, web of knowledge and Cochrane central register of Controlled Trials for literatures about the coadministration of statins and fibrates as the treatment of patients with dyslipidemia and type 2 diabetes mellitus. We included re-lated randomized controlled trials, controlled clinical trials and cross-sectional studies and excluded animal trials and clinical observations. The primary endpoints outcomes were the concentration of plasma total cholesterol （TC）, triglyc-eride （TG）, high density lipoprotein cholesterol （HDL-C） and low density lipoprotein cholesterol （LDL-C）. The secondary outcomes were cardiovascular diseases （CVD） and adverseevents.RESULTS： Ten studies were included in this meta-analysis. For lipid modifying efficacy, the combination of statins and fibrates therapy had more significant effecton reducing TC [ P = 0.004, weighted mean difference （WMD） = -8.19, 95%CI： -13.82--2.56] and TG concentra-tion （P 〈 0.001, WMD = -47.29, 95%CI： -68.66--25.92） and increasing HDL-C concentration （P 〈 0.00001, WMD = 3.79, 95%CI： 2.25-5.33） when compared with statins monotherapy, while the effect of reducing LDL-C concen-tration （ P = 0.50, WMD = -2.52, 95%CI： -9.76-4.72） was insignificant. To fibrates monotherapy, the combination therapy was more effective on reducing TC （ P 〈 0.00001, WMD = -48.51, 95%CI： -57.14--39.89）, TG （ P 〈 0.00001, WMD = -26.07, 95%CI： -30.96--21.18）, LDL-C concentra-tion （ P 〈 0.00001, WMD = -45.74, 95%CI： -53.35--38.13） and increasing HDL-C concentration （ P = 0.04, WMD = 1.38, 95%CI： 0.04-2.73）. For cardiovascular diseases, the coad-ministration therapy had no signifcant effect on reducing the incidence of these events when compared with mono-therapy （For primary clinical endpoints, P = 0.12, OR = 0.61, 95%CI： 0.33-1.14）; for secondary clinical endpoints, P =0.13, OR = 0.66, 95%CI： 0.38-1.14）. For adverse events happened during the follow-up, both the incidence of hepatic-related （alanine aminotransferase and/or aspartate aminotransferase of patients were ≥ 3 times of upper limit of normal） （ P = 0.38, OR = 0.55, 95%CI： 0.15-2.06） and muscular-related （myopathy and/or creatine phosphokinase ≥ 3 times of upper limit of normal） adverse events （P = 0.10, OR = 1.62, 95%CI： 0.91-2.86） had no signifcant dif-ference between these two therapies.CONCLUSION： The results showed statins-fbrates com-bination therapy was more effective on lipid modification and well tolerated but there was no significant effect on preventing cardiovascular diseases.

AIM: To evaluate the efficacy,effect of preventing cardiovascular diseases and safety of statins-fibrates combination therapy in diabetic dyslipidemia patients.METHODS: We searched the databases of MEDLINE,EMBASE,web of knowledge and Cochrane central register of Controlled Trials for literatures about the coadministration of statins and fibrates as the treatment of patients with dyslipidemia and type 2 diabetes mellitus.We included related randomized controlled trials,controlled clinical trials and cross-sectional studies and excluded animal trials and clinical observations.The primary endpoints outcomes were the concentration of plasma total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C).The secondary outcomes were cardiovascular diseases(CVD) and adverse events.RESULTS: Ten studies were included in this metaanalysis.For lipid modifying efficacy,the combination of statins and fibrates therapy had more significant effecton reducing TC [P = 0.004,weighted mean difference(WMD) =-8.19,95%CI:-13.82--2.56] and TG concentration(P < 0.001,WMD =-47.29,95%CI:-68.66--25.92) and increasing HDL-C concentration(P < 0.00001,WMD = 3.79,95%CI: 2.25-5.33) when compared with statins monotherapy,while the effect of reducing LDL-C concentration(P = 0.50,WMD =-2.52,95%CI:-9.76-4.72) was insignificant.To fibrates monotherapy,the combination therapy was more effective on reducing TC(P < 0.00001,WMD =-48.51,95%CI:-57.14--39.89),TG(P < 0.00001,WMD =-26.07,95%CI:-30.96--21.18),LDL-C concentration(P < 0.00001,WMD =-45.74,95%CI:-53.35--38.13) and increasing HDL-C concentration(P = 0.04,WMD = 1.38,95%CI: 0.04-2.73).For cardiovascular diseases,the coadministration therapy had no significant effect on reducing the incidence of these events when compared with monotherapy(For primary clinical endpoints,P = 0.12,OR = 0.61,95%CI: 0.33-1.14); for secondary clinical endpoints,P = 0.13,OR = 0.66,95%CI: 0.38-1.14).For adverse events happened during the follow-up,both the incidence of hepatic-related(alanine aminotransferase and/or aspartate aminotransferase of patients were ≥ 3 times of upper limit of normal)(P = 0.38,OR = 0.55,95%CI: 0.15-2.06) and muscular-related(myopathy and/or creatine phosphokinase ≥ 3 times of upper limit of normal) adverse events(P = 0.10,OR = 1.62,95%CI: 0.91-2.86) had no significant difference between these two therapies.CONCLUSION: The results showed statins-fibrates combination therapy was more effective on lipid modification and well tolerated but there was no significant effect on preventing cardiovascular diseases.