A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes

OBJECTIVE: This open-label, active-controlled study investigated the cardiac safety and antihyperglycemic effect of rosiglitazone (RSG) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Of the 203 patients randomly assigned to RSG (4 mg b.i.d.) or glyburide (GLB) (titrated to achieve optimal glycemic control for the first 8 weeks only to limit the risk of hypoglycemia; mean 10.5 mg/day), 118 had an echocardiogram performed at week 52. Left ventricular (LV) mass index, ejection fraction, and left ventricular end-diastolic volume were assessed by M-mode echocardiography at baseline and weeks 12, 28, and 52; 24-h ambulatory blood pressure was assessed at baseline and at weeks 28 and 52. Glycemic control was assessed by measuring fasting plasma glucose (FPG) and HbA(1c). RESULTS: Neither treatment produced an increase in LV mass index that exceeded 1 SD. Ejection fraction did not change in either group. Both groups had clinically insignificant increases in LV end-diastolic volume. RSG, but not GLB, caused a statistically significant reduction in ambulatory diastolic blood pressure. Both treatments reduced HbA(1c) and FPG. CONCLUSIONS: A total of 52 weeks of therapy with RSG (4 mg b.i.d.) did not adversely affect cardiac structure or function in patients with type 2 diabetes and produced significant and sustained reductions in hyperglycemia. Decreases in ambulatory diastolic blood pressure with RSG were superior to those with GLB.     

A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone

OBJECTIVE: To characterize potential differences in glycemic control, plasma lipid level, and weight in a cohort of patients previously treated with troglitazone (TROG) who were switched to either pioglitazone or rosiglitazone. RESEARCH DESIGN AND METHODS: After a 2-week washout from TROG, 186 patients were randomly assigned to receive either pioglitazone (PIO) or rosiglitazone (ROSI). Weight, HbA(1c), and fasting lipid profile were documented before discontinuing TROG and at 4 months after starting either pioglitazone or rosiglitazone. Secondarily, the effect of concurrent medications on study outcomes was assessed. RESULTS: A total of 127 patients completed follow-up: 67 individuals in the PIO group (32 women, 35 men) and 60 individuals in the ROSI group (33 women, 27 men). There were no significant differences in gender mix, age, weight, fasting lipid profile, or HbA(1c) between the ROSI and PIO groups. After 4 months of randomized treatment, no change in HbA(1c) from baseline between or within groups was noted. Both groups experienced an equal and significant increase in weight from baseline of approximately 2.0 kg. Thiazolidinedione and HMG-CoA reductase inhibitor therapy had significant and independent effects on lipid profile (P < 0.005). Significant improvements in lipid profile were noted in the PIO group (P < 0.01), whereas none were detected with conversion to ROSI. Specifically, the PIO group experienced an average decrease in total cholesterol of approximately 20 mg/dl. CONCLUSIONS: Differing effects on lipid profile were apparent after random conversion from TROG to either PIO or ROSI, despite similar weight increase and glycemic control. The clinical significance of these differences remains to be determined, and further comparative research is warranted.     

Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes

OBJECTIVE: To determine the efficacy of rosiglitazone compared with placebo in reducing hyperglycemia. RESEARCH DESIGN AND METHODS: After a 4-week placebo run-in period, 959 patients were randomized to placebo or rosiglitazone (total daily dose 4 or 8 mg) for 26 weeks. The primary measure of efficacy was change in the HbA1c concentration. RESULTS: Rosiglitazone produced dosage-dependent reductions in HbA1c of 0.8, 0.9, 1.1, and 1.5% in the 4 mg o.d., 2 mg b.i.d., 8 mg o.d., and 4 mg b.i.d. groups, respectively, compared with placebo. Clinically significant decreases from baseline in HbA1c were observed in drug-naive patients at all rosiglitazone doses and in patients previously treated with oral monotherapy at rosiglitazone 8 mg o.d. and 4 mg b.i.d. Clinically significant decreases from baseline in HbA1c were also observed with rosiglitazone 4 mg b.i.d. in patients previously treated with combination oral therapy. Approximately 33% of drug-naive patients treated with rosiglitazone achieved HbA1c < or =7% at study end. The proportions of patients with at least one adverse event were comparable among the rosiglitazone and placebo groups. There was no evidence of hepatotoxicity in any treatment group. There were statistically significant increases in weight and serum lipids in all rosiglitazone treatment groups compared with placebo. For LDL and HDL cholesterol, the observed increase appeared to be dose related. CONCLUSIONS: Rosiglitazone at total daily doses of 4 and 8 mg significantly improved glycemic control in patients with type 2 diabetes and was well tolerated.     

Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records

BACKGROUND: The antihyperglycemic effects of pioglitazone hydrochloride and rosiglitazone maleate are well documented. The results of clinical trials and observational studies have suggested, however, that there are individual differences in the effects of these drugs on blood lipid levels. OBJECTIVE: The present study evaluated the effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus. METHODS: This was a retrospective review of randomly selected medical records from 605 primary care practices in the United States in which adults with type 2 diabetes received pioglitazone or rosiglitazone between August 1, 1999, and August 31, 2000. The outcome measures were mean changes in serum concentrations of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glycosylated hemoglobin (HbA1c) values. RESULTS: Treatment with pioglitazone was associated with a reduction in mean TG of 55.17 mg/dL, a reduction in TC of 8.45 mg/dL, an increase in HDL-C of 2.65 mg/dL, and a reduction in LDL-C of 5.05 mg/dL. Treatment with rosiglitazone was associated with a reduction in mean TG of 13.34 mg/dL, an increase in TC of 4.81 mg/dL, a reduction in HDL-C of 0.12 mg/dL, and an increase in LDL-C of 3.56 mg/dL. With the exception of HDL-C, the differences in mean changes in lipid parameters between treatment groups were statistically significant (P < 0.001, pioglitazone vs rosiglitazone). Reductions in HbA1c were statistically equivalent between treatments (1.04% pioglitazone, 1.18% rosiglitazone). CONCLUSIONS: Treatment with pioglitazone was associated with greater beneficial effects on blood lipid levels than treatment with rosiglitazone, whereas glycemic control was equivalent between the 2 treatments.     

A randomized,double-blind,placebo-controlled,clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus

OBJECTIVE: The goal of this study was to compare the effects of 2 doses of pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo on glycated hemoglobin (HbA(1c)), insulin sensitivity, and lipid profiles in patients with type 2 diabetes mellitus who had suboptimal glycemic control and mild dyslipidemia. METHODS: Patients with type 2 diabetes mellitus (HbA(1c) >/=6.5% and /=7% to <8%) or high (>/=8% to 相似文献   

Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes

OBJECTIVE: The hypothesis that pioglitazone treatment is superior to gliclazide treatment in sustaining glycemic control for up to 2 years in patients with type 2 diabetes was tested. RESEARCH DESIGN AND METHODS: This was a randomized, multicenter, double-blind, double-dummy, parallel-group, 2-year study. Approximately 600 patients from 98 centers participated. Eligible patients had completed a previous 12-month study and consented to continue treatment for a further year. To avoid selection bias, all patients from all centers were included in the primary analysis (a comparison of the time-to-failure distributions of the two groups by using a log-rank test) regardless of whether they continued treatment for a 2nd year. By using repeated-measures ANOVA, time course of least square means of HbA(1c) and homeostasis model of assessment (HOMA) indexes (HOMA-%S and HOMA-%B) were analyzed. RESULTS: A greater proportion of patients treated with pioglitazone maintained HbA(1c) <8% over the 2-year period than those treated with gliclazide. A difference between the Kaplan-Meier curves was apparent as early as week 32 and widened at each time point thereafter, becoming statistically significant from week 52 onward. At week 104, 129 (47.8%) of 270 pioglitazone-treated patients and 110 (37.0%) of 297 gliclazide-treated patients maintained HbA(1c) <8%. Compared with gliclazide treatment, pioglitazone treatment produced a larger decrease in HbA(1c), a larger increase in HOMA-%S, and a smaller increase in HOMA-%B during the 2nd year of treatment. CONCLUSIONS: Pioglitazone is superior to gliclazide in sustaining glycemic control in patients with type 2 diabetes during the 2nd year of treatment.     

Metabolic and hemodynamic effects of pioglitazone in obese patients with type 2 diabetes

The purpose of the study was to evaluate the effectiveness and safety of pioglitazon, a hypoglycemizing preparation belonging to the group of thiazolidinediones, in treatment of diabetes mellitus (DM) type 2. Twenty DM type 2 patients were included in the study. The use of pioglitazon during 12 weeks resulted in a significant decrease in glycated hemoglobin, fasting glycemia, and postprandial reduction in insulinemia and insulinoresistance index HOMA-IR, as well as an improvement of lipid blood spectrum and the lessening of visceral obesity. Besides, a positive effect on arterial pressure was noted. The study revealed no significant adverse effects; good tolerance to treatment was noted in 90% of the patients.     

Additive effects of glucagon-like peptide 1 and pioglitazone in patients with type 2 diabetes

OBJECTIVE: To evaluate the effect of combination therapy with pioglitazone and glucagon-like peptide (GLP)-1 in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Eight patients with type 2 diabetes (BMI 32.7 +/- 1.3 kg/m(2) and fasting plasma glucose 13.5 +/- 1.2 mmol/l) underwent four different treatment regimens in random order: saline therapy, monotherapy with continuous subcutaneous infusion of GLP-1 (4.8 pmol x kg(-1) x min(-1)), monotherapy with pioglitazone (30-mg tablet of Actos), and combination therapy with GLP-1 and pioglitazone. The observation period was 48 h. End points were plasma levels of glucose, insulin, glucagon, free fatty acids (FFAs), and sensation of appetite. RESULTS: Fasting plasma glucose decreased from 13.5 +/- 1.2 mmol/l (saline) to 11.7 +/- 1.2 (GLP-1) and 11.5 +/- 1.2 (pioglitazone) and further decreased to 9.9 +/- 1.0 (combination) (P < 0.001). Eight-hour mean plasma glucose levels were reduced from 13.7 +/- 1.1 mmol/l (saline) to 10.6 +/- 1.0 (GLP-1) and 12.0 +/- 1.2 (pioglitazone) and were further reduced to 9.5 +/- 0.8 (combination) (P < 0.0001). Insulin levels increased during monotherapy with GLP-1 compared with monotherapy with pioglitazone (P < 0.01). Glucagon levels were reduced in GLP-1 and combination therapy compared with saline and monotherapy with pioglitazone (P < 0.01). FFAs during breakfast (area under the curve, 0-3 h) were reduced in combination therapy compared with saline (P = 0.03). Sensation of appetite was reduced during monotherapy with GLP-1 and combination therapy (P < 0.05). CONCLUSIONS: GLP-1 and pioglitazone show an additive glucose-lowering effect. A combination of the two agents may, therefore, be a valuable therapeutic approach for the treatment of type 2 diabetes.     

A randomized comparison of pioglitazone to inhibit restenosis after coronary stenting in patients with type 2 diabetes

OBJECTIVE: Recent studies have demonstrated that the treatment with thiazolidinediones reduces in-stent restenosis. The aim of this study was to elucidate the mechanism of the efficacy of pioglitazone for preventing in-stent restenosis in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a prospective, randomized trial involving 54 type 2 diabetic patients referred for coronary stenting who were randomly assigned to either the control or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months follow-up. Endothelial nitric oxide synthase (eNOS), tumor necrosis factor alpha, interleukin-6, leptin, and adiponectin were measured at study entry and at 6 months follow-up. RESULTS: A total of 28 patients were randomly assigned to the control group, and 26 patients were assigned to the pioglitazone group. There were no significant differences in glycemic control levels or in lipid levels in the two groups at baseline or at follow-up. Insulin, homeostasis model assessment of insulin resistance, eNOS, and leptin at follow-up were significantly reduced in the pioglitazone group compared with the control group. The late luminal loss and in-stent restenosis were significantly less in the pioglitazone group than in the control group. Leptin independently correlated with late luminal loss at multiple regression analysis. CONCLUSIONS: The treatment with pioglitazone in type 2 diabetic patients significantly reduced leptin. This decreased leptin improved insulin resistance and endothelial function with the reduction of insulin. The improved endothelial function affected the reduction of in-stent restenosis.     

Withdrawal of pioglitazone in patients with type 2 diabetes mellitus

Background and objective: The remodelling of the adipose tissue by pioglitazone may be associated with the sustained therapeutic effects. We studied the effects of withdrawal of pioglitazone after 3‐month treatment on glucose, lipid and high‐molecular weight (HMW) adiponectin levels as well as liver function in patients with type 2 diabetes mellitus. Methods: Forty‐nine Japanese patients with type 2 diabetes mellitus were randomly assigned into the withdrawal group after 3‐month treatment with pioglitazone (15 or 30 mg daily) and the non‐withdrawal group. Results and discussion: Three‐month treatment with pioglitazone improved glycaemic control, homeostasis model assessment for insulin resistance (HOMA), dyslipidaemia and liver function tests in association with a marked increase in serum HMW adiponectin level. Three months later after the withdrawal of pioglitazone, however, fasting plasma glucose and HOMA increased, whereas serum HMW adiponectin decreased to the pretreatment levels. Dyslipidaemia also returned to the pretreatment level. On the other hand, liver enzymes at 3 months after the withdrawal remained lower after a mild rebound. In addition, the bone formation marker, serum bone‐specific alkaline phosphatase, was significantly reduced by pioglitazone treatment in post‐menopausal women. Conclusions: The present study suggests that 3‐month treatment with pioglitazone has no sustained beneficial effects except in liver function tests in patients with type 2 diabetes mellitus.     

老年男性2型糖尿病患者并发动脉粥样硬化与罗格列酮的干预效应

目的：探讨噻唑烷二酮类药物对老年男性2型糖尿病患者的抗动脉粥样硬化作用,并了解该种作用发生的相关因素.方法：①选择2002-03/2003-03哈尔滨医科大学附属第二医院老年病科门诊就诊的男性2型糖尿病患者45例.符合纳入标准的2型糖尿病患者24例,均签署知情同意书.随机将受试者分为3组：对照组（给予格列吡嗪5 mg/次,3次/d）,罗格列酮4 mg/d组（给予罗格列酮4 mg/次,1次/d）和罗格列酮8 mg/d组（给予罗格列酮8 mg/d）,每组8例.本实验共进行6个月.根据罗格列酮治疗3个月糖化血红蛋白下降的情况又分为2亚组：反应亚组（n=10,下降＞1%为反应亚组）和非反应亚组（n=6,下降＜1%为非反应亚组）.②于服药前,服药后3,6个月分别测定身高、体质量、收缩压、舒张压、空腹血糖、糖化血红蛋白、空腹血浆胰岛素、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、三酰甘油及高敏C反应蛋白、纤维蛋白原和颈动脉内膜中层厚度.并计算胰岛素抵抗指数和体质量指数.血浆胰岛素采用双相、双步时间依赖性荧光免疫法测定.高敏C反应蛋白运用比浊法检测.纤维蛋白原运用CA-1500全自动血栓/止血测定系统枸橼酸抗凝血浆检测.颈动脉内膜中层厚度应用高分辨B-型超声仪测定.③各组间比较应用方差分析,组内治疗前后比较应用HotellingT2检验.应用Pearsson相关分析和多元线性回归分析影响颈动脉内膜中层厚度的因素.结果：实验过程中无因肝肾功能改变以及药物不耐受而退出试验者,24例均进入结果分析.①对照组治疗3和6个月后空腹血糖,糖化血红蛋白,三酰甘油水平明显低于治疗前（P＜0.01）,其余指标无显著改变.罗格列酮治疗组在治疗3和6个月后空腹血糖、糖化血红蛋白、胰岛素抵抗指数、三酰甘油、纤维蛋白原,C反应蛋白和颈动脉内膜中层厚度明显低于治疗前（P＜0.05～0.01）;罗格列酮治疗组治疗后空腹胰岛素下降,但治疗6个月时才明显低于治疗前和对照组（P＜0.01）;罗格列酮治疗组治疗6个月后空腹胰岛素明显低于治疗3个月后（P＜0.01）,罗格列酮4mg/d治疗组治疗6个月后胰岛素抵抗指数较治疗3个月后明显减少（P＜0.05）,其余指标于治疗3和6个月后差异不明显.②反应亚组和非反应亚组治疗3和6个月后胰岛素抵抗指数、三酰甘油、纤维蛋白原、C反应蛋白、颈动脉内膜中层厚度均明显低于治疗前（P＜0.01）,且除胰岛素抵抗指数外上述各项二亚组间差异不明显.反应亚组治疗3和6个月后空腹血糖、糖化血红蛋白、空腹胰岛素、胰岛素抵抗指数、三酰甘油、纤维蛋白原、C反应蛋白、颈动脉内膜中层厚度均较低于治疗前（P＜0.01）,空腹血糖、糖化血红蛋白明显低于非反应亚组（P＜0.05～0.01）,反应亚组治疗6个月后空腹胰岛素和胰岛素抵抗指数明显低于非反应亚组和治疗3个月后（P＜0.05～0.01）.反应亚组治疗6个月后低密度脂蛋白胆固醇水平明显高于非反应亚组和治疗前（P＜0.05,0.01）.③Pearson相关分析表明,颈动脉内膜中层厚度的变化只与C反应蛋白的变化呈显著正相关（r=0.298,P＜0.05）,而与糖化血红蛋白、胰岛素抵抗指数等指标改变不相关（r=-0.018,-0.218,P＞0.05）.多元线性回归分析也显示颈动脉内膜中层厚度只与C反应蛋白相关（回归系数b=0.435,P＜0.05）,而与糖脂代谢指标无关.结论：罗格列酮的抗动脉粥样硬化作用主要依赖于其降糖外作用,并可能与抗炎作用有关,此作用无剂量和时间依赖性.     

One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes

OBJECTIVE: The goal was to assess the 1-year efficacy and safety of the addition of pioglitazone or metformin to existing sulfonylurea (SU) therapy in patients with inadequately controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: In this multicenter, double-blind study, patients were randomized to receive either pioglitazone 15 mg (n = 319) or metformin 850 mg (n = 320) and up to 45 mg/day and 2,550 mg/day, respectively. The primary efficacy endpoint was HbA(1c) at week 52. Fasting plasma glucose, insulin, and lipid profiles were also measured. RESULTS: HbA(1c) was reduced by 1.20% in the SU plus pioglitazone group and 1.36% in the SU plus metformin group, and fasting plasma glucose was reduced by 2.2 and 2.3 mmol/l in the respective groups. Fasting insulin levels were also reduced (pioglitazone arm -1.3 micro IU/ml; metformin arm -0.8 micro IU/ml). There were no significant between-treatment differences in these three parameters. Pioglitazone addition to SU significantly reduced triglycerides (-16 vs. -9%; P = 0.008) and increased HDL cholesterol (14 vs. 8%; P < 0.001) compared with metformin addition. LDL cholesterol was increased 2% by the addition of pioglitazone and decreased 5% by the addition of metformin to SU (P < 0.001). Urinary albumin-to-creatinine ratio was reduced by 15% in the SU plus pioglitazone group and increased 2% in the SU plus metformin group (P = 0.017). Both combinations were well tolerated with no evidence of hepatic or cardiac toxicity in either group. CONCLUSIONS: Clinically equivalent improvements in glycemic control were observed for both combinations. Compared with metformin plus SU, addition of pioglitazone to SU resulted in a reduction of the urinary albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and significantly greater improvements in triglyceride levels and HDL cholesterol levels. Metformin plus SU was associated with a significant reduction in LDL cholesterol. SU plus pioglitazone is an effective and well-tolerated combination regimen that may provide additional beneficial effects for patients with type 2 diabetes.     

老年男性2型糖尿病患者并发动脉粥样硬化与罗格列酮的干预效应

目的:探讨噻唑烷二酮类药物对老年男性2型糖尿病患者的抗动脉粥样硬化作用,并了解该种作用发生的相关因素。方法:①选择2002-03/2003-03哈尔滨医科大学附属第二医院老年病科门诊就诊的男性2型糖尿病患者45例。符合纳入标准的2型糖尿病患者24例,均签署知情同意书。随机将受试者分为3组:对照组(给予格列吡嗪5mg/次,3次/d),罗格列酮4mg/d组(给予罗格列酮4mg/次,1次/d)和罗格列酮8mg/d组(给予罗格列酮8mg/d),每组8例。本实验共进行6个月。根据罗格列酮治疗3个月糖化血红蛋白下降的情况又分为2亚组:反应亚组(n=10,下降>1%为反应亚组)和非反应亚组(n=6,下降<1%为非反应亚组)。②于服药前,服药后3,6个月分别测定身高、体质量、收缩压、舒张压、空腹血糖、糖化血红蛋白、空腹血浆胰岛素、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、三酰甘油及高敏C反应蛋白、纤维蛋白原和颈动脉内膜中层厚度。并计算胰岛素抵抗指数和体质量指数。血浆胰岛素采用双相、双步时间依赖性荧光免疫法测定。高敏C反应蛋白运用比浊法检测。纤维蛋白原运用CA-1500全自动血栓/止血测定系统枸橼酸抗凝血浆检测。颈动脉内膜中层厚度应用高分辨B-型超声仪测定。③各组间比较应用方差分析,组内治疗前后比较应用HotellingT2检验。应用Pearsson相关分析和多元线性回归分析影响颈动脉内膜中层厚度的因素。结果:实验过程中无因肝肾功能改变以及药物不耐受而退出试验者,24例均进入结果分析。①对照组治疗3和6个月后空腹血糖,糖化血红蛋白,三酰甘油水平明显低于治疗前(P<0.01),其余指标无显著改变。罗格列酮治疗组在治疗3和6个月后空腹血糖、糖化血红蛋白、胰岛素抵抗指数、三酰甘油、纤维蛋白原,C反应蛋白和颈动脉内膜中层厚度明显低于治疗前(P<0.05～0.01);罗格列酮治疗组治疗后空腹胰岛素下降,但治疗6个月时才明显低于治疗前和对照组(P<0.01);罗格列酮治疗组治疗6个月后空腹胰岛素明显低于治疗3个月后(P<0.01),罗格列酮4mg/d治疗组治疗6个月后胰岛素抵抗指数较治疗3个月后明显减少(P<0.05),其余指标于治疗3和6个月后差异不明显。②反应亚组和非反应亚组治疗3和6个月后胰岛素抵抗指数、三酰甘油、纤维蛋白原、C反应蛋白、颈动脉内膜中层厚度均明显低于治疗前(P<0.01),且除胰岛素抵抗指数外上述各项二亚组间差异不明显。反应亚组治疗3和6个月后空腹血糖、糖化血红蛋白、空腹胰岛素、胰岛素抵抗指数、三酰甘油、纤维蛋白原、C反应蛋白、颈动脉内膜中层厚度均较低于治疗前(P<0.01),空腹血糖、糖化血红蛋白明显低于非反应亚组(P<0.05～0.01),反应亚组治疗6个月后空腹胰岛素和胰岛素抵抗指数明显低于非反应亚组和治疗3个月后(P<0.05～0.01)。反应亚组治疗6个月后低密度脂蛋白胆固醇水平明显高于非反应亚组和治疗前(P<0.05,0.01)。③Pearson相关分析表明,颈动脉内膜中层厚度的变化只与C反应蛋白的变化呈显著正相关(r=0.298,P<0.05),而与糖化血红蛋白、胰岛素抵抗指数等指标改变不相关(r=-0.018,-0.218,P>0.05)。多元线性回归分析也显示颈动脉内膜中层厚度只与C反应蛋白相关(回归系数b=0.435,P<0.05),而与糖脂代谢指标无关。结论:罗格列酮的抗动脉粥样硬化作用主要依赖于其降糖外作用,并可能与抗炎作用有关,此作用无剂量和时间依赖性。     

Long-term glycaemic control with pioglitazone in patients with type 2 diabetes

Patients with type 2 diabetes have dual defects: insulin resistance and beta-cell dysfunction. Thiazolidinediones (TZDs), a new class of oral drugs used for the treatment of type 2 diabetes, reduce insulin resistance via an action on peroxisome proliferator-activated receptors. There is also growing evidence that TZDs may preserve beta-cell function. Pioglitazone is a TZD that provides appropriate monotherapy or combination treatment for patients with type 2 diabetes. Studies of up to 32-week duration have shown that pioglitazone significantly reduces HbA1c and fasting plasma glucose when used alone or in combination with another glucose-lowering agent. Four recently published 52-week clinical trials, involving over 3700 patients with type 2 diabetes, show that pioglitazone is an effective long-term treatment, both as monotherapy and in combination with metformin or sulphonylurea. As well as maintaining glycaemic control over the long term, pioglitazone also confers benefits in terms of improvements in fasting insulin, lipid parameters, C-peptide and 32,33-split proinsulin (independent predictors of cardiovascular risk) and hypoglycaemia compared with other monotherapies or combination therapies. It is well tolerated, with a low incidence of adverse events. These long-term data support the concept that pioglitazone should be used earlier in the treatment of type 2 diabetes, either as monotherapy or as add-on therapy.     

Lipid effects of glyburide/metformin tablets in patients with type 2 diabetes mellitus with poor glycemic control and dyslipidemia in an open-label extension study

BACKGROUND: Because both type 2 diabetes and elevated plasma lipid levels are important independent risk factors for cardiovascular disease and coronary heart disease, the choice of an antihyperglycemic agent for patients with type 2 diabetes--in whom abnormal plasma lipid levels are often seen-should take into account effects on lipids as well as on markers of glycemic control. OBJECTIVE: This study assessed the effects on lipid levels of glyburide/metformin tablets in the treatment of type 2 diabetes, particularly in a group of patients who had poor glycemic control and dyslipidemia at baseline. METHODS: This 52-week, open-label study was an extension of a 32-week, double-blind, placebo-controlled study. The patient population was drawn from 3 groups: those who completed the double-blind study, those who were discontinued from the double-blind study, and those who were ineligible for the double-blind study based on predefined measures of glycemic control (screening fasting plasma glucose > 240 mg/dL and glycosylated hemoglobin [HbA1c] < or = 12%, or HbA1c 11%-12%) and were directly enrolled in the open-label extension study. Patients with an HbA1c of < 9% received glyburide/ metformin tablets 1.25 mg/250 mg BID; those with an HbA1c > or = 9% received glyburide/ metformin tablets 2.5 mg/500 mg BID. Changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels were assessed for 52 weeks. RESULTS: The study population included 828 patients: 515 who completed the double-blind study, 138 who were discontinued from the double-blind study, and 175 who were enrolled directly. Direct enrollees had poor glycemic control and dyslipidemia at baseline. Improvements in plasma lipid levels were seen as early as week 13. At week 52, the mean change in TC from baseline was -8.0 mg/dL for the total population (95% CI, -10.9 to -5.2; P < 0.05) and -23.2 mg/dL for direct enrollees (95% CI, -30.1 to -16.4; P < 0.05). The mean decrease in LDL-C from baseline for the total population was 2.86 mg/dL (95% CI, -5.3 to -0.4; P < 0.05), compared with a reduction of 13.3 mg/dL for direct enrollees (95% CI, -18.5 to -8.1; P < 0.05). Mean HDL-C levels were minimally affected. Mean TG levels decreased by 27.8 mg/dL for the entire population (95% CI, -42.9 to -12.8; P < 0.05) and by 99.7 mg/dL for direct enrollees (95% CI, -152.5 to -46.8; P < 0.05). CONCLUSION: In this open-label extension study, treatment with glyburide/ metformin tablets for type 2 diabetes had a durable, favorable effect on lipid levels, particularly in those with poor glycemic control and dyslipidemia at baseline.     

The effects of triple vs. dual and monotherapy with rosiglitazone, glimepiride, and atorvastatin on lipid profile and glycemic control in type 2 diabetes mellitus rats

The present study was undertaken to investigate the effects of triple oral therapy and different combination of rosiglitazone, atorvastatin, and glimepiride on streptozotocin (STZ)-induced diabetic rats. The various biochemical parameters studied included glycosylated hemoglobin (A1c), fasting plasma sugar levels, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol in diabetic and normal rats. The present study demonstrates that atorvastatin could increase the effect of rosiglitazone and glimepiride and lipid-lowering effect of combination of rosiglitazone and glimepiride (GLIM). According to our finding, similar results for rosiglitazone plus atorvastatin were obtained in terms of correcting lipid parameters, whereas the suppressive action of triple oral therapy of rosiglitazone and glimepiride, and atorvastatin on blood glucose, total cholesterol, LDL, VLDL, HDL cholesterol, and triglyceride was more beneficial than that of dual therapy of different combinations and monotherapy.