Systematic Reviews Of Drug Therapy Of The Metabolic Syndrome

Objietive: To evaluate the efficacy and safety of lipid-modifying agents for metabolism syndromeMethods: We searched the Cochrane Library (Issuel,2007), MEDLINE (1966 to February, 2007), EMBASE (1984 to 2007),the China Biological Medicine Database (1978 to February, 2007), VIP (1977 to February, 2007), CMAC(1994 to 2007) and hand-searched several related Chinese journals. Two reviewers independently screened the studies for eligibility, evaluated the quality and extracted the data from the eligible studies, with confirmation of cross-check. Different opinions would be decided by the third party. The quality of the included trials such as randomization, blind, allocation concealment and following-up was assessed. Meta-analysis was performed by RevMan 4.2.9 software. After heterogeneity test, data without heterogeneity could be pooled using fixed effect model, and those with heterogeneity could be solved by sensitivity analysis, subgroup analysis as well as randomized effect model. We will compare outcome measures for binary data using relative risks(RR) or odds ratio(OR) with 95% confidence intervals(CI). For continuous data, the weighted means difference (WMD) will be used.Results: Eleven studies involving 1422 patients with metabolic syndrome were included. Lipid-regulating drugs include statins, which are atorvastatin,simvastain, rosuvastatin, pravastatin, invovling 860 patients with metabolic syndrome, fibrates, which are fenofibrate, invovling 242 patients with metabolic syndrome, statins and fibrates in combination therapy invovling 320 patients with metabolic syndrome. In addition, eight post hoc analysis studies involving 10641 patients with metabolic syndrome were included. The results indicated that fenofibrate, compared with placebo, sigificantly improved flow-mediated dilation[WMD1.86, 95%CI (1.13,2.59)], TG[WMD-1.77, 95%CI (-2.21,-1.33)], HDL-c[WMD6.62, 95%CI (2.07, 11.17)], adiponectin and fibrinogen[WMD-50.0, 95%CI (-55.95,-44.05)]. Similar to atorvastatin, simvastatin significantly decreased TG values[WMD1.90, 95%CI (-4.48,8.28) ], whereas simvastatin was superior to atorvastatin in HDL-c improvement[WMD7.0, 95%CI (3.81,10.19)]. Rosuvastatin was similar to atorvastatin in improving TG[WMD-2.30, 95%CI(-7.87,3.27)] and hsCRP, while rosuvastatin was better than atorvastatin regarding HDL-c improvement [WMD4.60, 95%CI (1.54,7.66)]. No sigificant differences for atorvastatin, fenofibrate, alone or in combination, were found in prevalence of metabolic syndrome reduction[RR0.99, 95%CI (0.84,1.16); RR1.03, 95%CI(0.88,1.20); RR1.01, 95%CI (0.87,1.18)]. Atorvastatin as well as atorvastatin-fenofibrate combination was superior to fenofibrate alone in the improvement of hsCRP[WMD-1.0, 95%CI(-1.20,-0.80);WMD-1.20, 95%CI(-1.41,-0.99)] and effective rate for non-alcoholic fatty liver disease[RR1.59, 95%CI (1.13,2.24); RRI.68, 95%CI(1.20, 2.35)], whereas fenofibrate and atorvastatin- fenofibrate combination were superior to atorvastatin alone in fibrinogen improvement [WMD-50.0, 95%CI (-62.68,-37.32); WMD-53.0, 95%CI(-64.83,-41.17)]. The combination of atorvastatin-fenofibrate produced more effective than atorvastatin alone in improving TG[WMD-0.30, 95%CI(-0.56, -0.04)] and HDL-c[WMD7.77, 95%CI(3.87,11.67)], with fenofibrate similar to atorvastatin and atorvastatin-fenofibrate combination in TG [WMD-0.20, 95%CI(-0.47, 0.07);WMD-0.10,95%CI(-0.37,0.17)]andHDL-c[WMD3.88,95%CI(-0.02, 7.78); WMD3.89,95%CI(-0.33,8.11)] improvement. Simvastatin- fenofibrate combination showed signifiantly greater effective in the improvement of HDL-c[WMD6.0,95%CI(0.72,11.28)]andTG[WMD-1.06,95%CI(-1.80, -0.32)] compared with simvastatin alone. There was no significant differences in the prevalence of metabolic syndrome reduction [RR1.04, 95%CI(0.61, 1.76)land TG improvement between fenofibrate and fenofibrate-orlistat combination. The results of post hoc analysis: Simvastatin,compared with placebo, was associated with significant reduction in the incidence of the all-cause mortality[RR0.59, 95%CI (0.4,0.87)], cardiac mortality[RR0.42, 95%CI (0.26,0.69)] and CVD events [RR0.64, 95%CI (0.51,0.81)], as well as in improvement in HDL-c and TG. Compared with placebo, bezafibrate prdodvided more favourable effects on reducing the incidence of CVD events[RR 0.77, 95%CI (0.61,0.97) ] and myocardial infarction[RR 0.73, 95%CI (0.56,0.95)], as well as on improving HDL-c and TG. Atorvastatin 80mg was superior to atorvastatin 10mg in CVD events[RR0.73, 95%CI (0.63,0.85)] and cerebrovascular events[RR0.75,95%CI(0.60,0.94)] reduction, and TG improvement. However, there was no significant differences between atorvastatin 80mg and atorvastatinl0mg.regarding the all-cause mortality rate[RR0.97, 95%CI (0.79,1.19) ] in absence of favorable HDL-c effect for both medications. No significant differences between nicotinic acid and placebo was observed regarding the incidence of all-cause mortality[RR0.93, 95%CI (0.82,1.07)] and myocardial infarction events[RR0.33, 95%CI (0.11,1.02)], as well as the prevalence of metabolic syndrome reduction. Similar to atorvastatin, simvastatin significantly decreased the prevalence of metabolic syndrome [RR0.98, 95%CI (0.73,1.32)]. Both rosuvastatinl0mg and atorvastatin 20mg lowered significantly greater than simvastatin 20mg and pravastatin 40mg in TG[WMD-6.10, 95%CI(-10.52,-1.68);WMD-10.10 95%CI(-14.56, -5.64); WMD-6.60, 95%CI(-10.59,-2.61 );WMD-10.60 95%CI(-14.63,-6.57)].The clinical trails showed that majority of lipid-modulating drugs offered no positive effects on FPG, offered no positive effects on FPG, BP, BMI and WC, whose therapeutic effect on insulin sensitivity was uncertain. The side effects and adverse drug reactions for lipid-regulating drugs were mild to moderate, and well tolerated.Conclusions: Results suggested that lipid-regulating drugs exhibited benificial effect on TG and a certain effect on resolution of metabolic syndrome, improving HDL-c, vascular endothelial function, proinflammatory and prothrombotic milieu in the absence of favorable effect on blood glucose, blood pressure and central obesity for most of them. The clinial trials showed that the therapeutic effect of lipid-regulating drugs on the incidence of CVD events and mortality, insulin sensitivity is uncertain. Statins and fibrates in combination therapy, compared with each monotherapy, was more effictive in improving lipid parameters, without significant difference regading the resolution of metabolic syndrome,as well as the improvement of blood glucose, blood pressure, central obesity between monotherapy and combined drug therapy. There is insufficient evidence to recommend the use of lipid-modifying drugs in this review for metabolic syndrome due to low methodological quality, small sample size,and limited number of trails. More high quality, large-scale randomized controlled trials are required. Objietive: To evaluate the efficacy and safety of metformin for metabolism syndromeMethods: same as partâ… Results: seven trials involving a total of 2664 patients with metabolic syndrome have been analysed in this review. Metformin, compared with placebo, exhibited more favourable effect on reduction of the prevalence of metabolic syndrome [RR1.27,95%CI(1.01,1.60)]and the proportion of abdominal obesity, reduced HDL-c, elevated FPG[RR1.64, 95%CI(1.06,2.55); RR1.61, 95%CI(1.16,2.23); RR 1.55, 95%CI(1.17,2.05)], as well as on the improvement of FPG[WMD-0.90, 95% CI(-1.06,-0.74)], insulin sensitivity and flow-mediated dilation[RR 5.50,95%CI(4.37,6.63)].While there was no siginificant difference between metformin and placebo in decreasing the proportion of elevated TG, elevated BP[RR1.04, 95%CI(0.80,1.35); RR1.05, 95%CI(0.76,1.46)]. The addition to atenolol plus nitrendipine was superior to single atenolol plus nitrendipine in reduction of the proportion of high TG, abdominal obesity and IGT[RR5.57, 95%CI(1.56,19.84);RR14.47,95%CI(3.34,62.61);RR16.51,95%CI(6.06,45.0)]. Metformin was better than low-fat diet therapy in the improvement of FPG[WMD-0.64,95%CI(-0.88,-0.40)], 2 hour postload plasma glucose after OGTT[WMD-3.39, 95%CI(-4.48,-2.30)] and insulin sensitivity[WMD0.45, 95%CI(0.21,0.59)]. Metformin was similar to acarbose in TG[WMD-0.40, 95%CI(-1.37, 0.57)] and FPG[WMD0.01, 95%CI(-0.17,0.19)] improvement, whereas metformin was less effective than acarbose in 2 hour postload plasma glucose afte OGTT improvement [WMD1.44, 95%CI(1.10,1.78)]. The evidence indicated that metformin had no positive effects on BP, abdominal obesity and lipid parameters. The clinial trails did not report the adverse drug reactions for metformin.Conclusion: Results suggested that metformin associated with beneficial effect on reducing the proportion of high FPG, IGT and central obesity, as well as improving blood glucose, insulin sensitivity, with showing certain effect on the prevalence of metabolic syndrome decreased and vascular endothelial function improvement. The therapeutic effect of metformin on BP, obesity, lipid profile was unclear. Overall there is insufficient evidence to recommend the use of metformin in this review for metabolic syndrome due to low methodologial quality, small sample size, and limited number of trails. More high quality, large-scale randomized controlled trials are required. Objietive: To evaluate the efficacy and safety of thiazolidinediones for metabolism syndromeMethods: same as partâ… Results: Ten randomised controlled trials involving a total of 1183 patients with metabolic syndrome have been analysed in this systematic review. Thiazolidinediones included rosiglitazone in monotherapy invoving 822 patients With metabolic syndrome, pioglitazone in monotherapy involving 60 patients with metabolic syndrome and rosiglitazone-pioglitazone in combination therapy involving 293 patients with metabolic syndrome. In addition, two post hoc analysis studies, which involved 3186, 2218 patients with metabolic syndrome respectively, were included. Results suggested that there was no significant difference between rosiglitazone and placebo in occurrence of CVD events[RR0.50, 95%CI (0.25,1.00)] such as myocardial infarction and urgent vessel revascularization after coronary stent implantation in patients with metabolic syndrome. Rosiglitazone significantly decreased the prevalence of metabolic syndrome[RR4.0, 95%CI(1.63,9.82)] and improved insulin sensitivity[WMD-0.80, 95%CI(-0.90,-0.70)], flow-mediated dilation[WMD4.20, 95%CI (3.92, 4.48)], hsCRP[WMD-0.90, 95%CI(-0.99,-0.81)], resistin and a iponectin as compared with placebo. Compared with placebo,pioglitazone showed siginificant improvement in insulin sensitivity[WMD0.02, 95%CI (0.01,0.03)], HDL-c[WMD0.02, 95%CI(0.01,0.03)], hsCRP, adiponectin [WMD 10.90,95%CI(6.30, 15.50)] and resistin. Pioglitazone plus glimepirde glimepirde was superior to rosiglitazone plus glimepiride in improving TG[WMD-64.0,95%CI(-78.71,-49.29)] and HDL-c[WMD5.0,95%CI(2.90,7.10)], with no significant difference in improving BP[SBP:WMD0.60,95%CI (-1.15,2.35); DBP:WMD1.60,95%CI(-0.27, 3.47)], FPG[WMD0.0, 95% CI(-13.64, 13.64)], PPG, HbAlc, insulin sensitivity[WMD0.20, 95%CI(-1.07,1.47)] and PAI-1[WMD 2.10,95%CI(-5.46,9.66)] for both treatment. The combination of rosiglitazone with metformin was similar to pioglitazone- metformin combination in improving FPG[WMD5.0,95%CI(2.57,7.43)], PPG, HbAlc and insulin sensitivity[WMD-0.80, 95%CI(-2.96,1.36)], whereas pioglitazone plus metformin significantly improved TG[WMD-39.0,95%CI(-53.82,-24.18)] and HDL-c[WMD5.0,95%CI(2.57,7.43)] more than did rosiglitazone plus metformin. Results of post hoc analysis:With no significantdifference between pioglitazone and metformin in resolution of metabolic syndrome[RR0.88, 95%CI(0.69,1.11)], pioglitazone hada more effective than metformin in decreasing the proportion of low HDL-c[RR0.88, 95%CI(0.69,1.11)], as well as in improving insulin sensitivity[WMD-1.20, 95%CI(-1.72,-0.68)], HDL-c[WMD -1.20, 95%CI(-1.72,-0.68)], TG[WMD-10.20,95%CI(-14.91,-5.94)], FPG[WMD-10.20,95%CI(-14.91,-5.94)] and 2 hour postload plasma glucose after OGTT. There was no sigificant difference between pioglitazone-sulphanylurea combination and metformin-sulphanylurea combination in the prevalence of metabolic syndrome reduction[RR0.93,95%CI(0.63,1..39)], as well as in insulin sensitivity[WMD-0.30,95%CI(-1.12,0.52)], TG[WMD-6.20,95%CI(-13.64,1.24)] and FPG[WMD0.10,95%CI(-7.32, 7.52)] improvment. Whereas pioglitazone plus sulphanylurea was superior to metformin plus sulphanylurea in decreasing the proportion of low HDL-c[RR1.39,95%CI (1.04,1.85)] and improving HDL-c[WMD5.80, 95%CI(2.64,8.96)] and 2 hour postload plasma glucose afer OGTT. The results of included clinical trails showed that the effect of rosiglitazone and pioglitazone, alone or in combination, were uncertain on BE Rosiglitazone and pioglitazone, alone or in combination with sulphanylureas, had no favorable effect on BMI and WC, or resulted in weight gain. The adverse drug reactions for thiazolidinediones were mild to moderate, and well tolerated.Conclusion: Results suggested that thiazolidinediones produced positive effect on improvement of blood glucose, insulin sensitivity, proinflammary milieu, and vascular endothelial function in the absence of favorable cental obesity effects or resulting in negative weight gain effects. Thiazolidinediones showed a certain effect on decreasing the prevalence of metabolic syndrome and improving prothrombotic milieu, adiponectin and resistin. Pioglitazone was associated with beneficial effects on reduction of the proportion of low HDL-c, as well as on HDL-c improvment. The therapeutic effect of thiazolidinediones on BP was uncertain. Overall there is insufficient evidence to recommend the use of thiazolidinediones in this review for metabolic syndrome due to low methodologial quality, small sample size, and limited number of trails. More high quality, large-scale randomized controlled trials are required.