Translating science into clinical practice: focus on vildagliptin in combination with metformin

Vildagliptin is a potent and selective oral dipeptidyl peptidase-4 inhibitor that improves glycaemic control in patients with type 2 diabetes mellitus (T2DM) by increasing both α- and β-cell responsiveness to glucose. The efficacy, tolerability and safety of the combination of vildagliptin and metformin in the treatment of T2DM have been established in numerous trials in the extensive vildagliptin clinical programme. As add-on therapy in patients with inadequate glycaemic control on metformin, vildagliptin produces clinically significant reductions in glycated haemoglobin (HbA1c) and fasting plasma glucose, is well tolerated, and is associated with absence of weight gain and minimal risk of hypoglycaemia. Compared with thiazolidinedione add-on treatment, vildagliptin is associated with similar significant reductions in HbA1c without the weight gain seen with the former. Compared with sulfonylurea add-on treatment, vildagliptin is associated with similar efficacy in controlling glycaemia but absence of weight gain and a markedly lower risk of hypoglycaemia. In drug-naïve patients, single-tablet combinations of vildagliptin/metformin 50/500 and 50/1000 mg bid produced significantly greater reductions in HbA1c than monotherapy with either agent and were well tolerated, with no weight gain and minimal risk of hypoglycaemia. The combination of vildagliptin and metformin poses numerous advantages in the treatment of T2DM.     

Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin.

AIMS: To assess the effects and safety of increasing sulphonylurea dosages or adding metformin in poorly controlled elderly Type 2 diabetic patients. METHODS: A 18-month multicentre clinical study was performed on sulphonylurea-treated diabetic patients over 70 years of age with well-preserved renal function, steady fasting blood glucose > or = 200 mg/dl and HbA1c > or = 9%. Patients were randomly assigned to sulphonylurea increased up to its maximum dosage (1st group) or to addition of metformin (2nd group). Glycaemic control, lipid pattern, haemostatic status and safety were monitored during run-in, at baseline and at scheduled intervals for 18 months. Results refer to 85 patients in the 1st group and 89 patients in the 2nd with complete data. RESULTS: Similar improvements in glycaemic levels were observed with both treatments within the first month and a similar decrease in HbA1c within the third month. No further changes occurred in glycaemic control. In the 1st group, fasting glucose (mmol/l, mean +/- SE) decreased from 14.21 +/- 0.49 to 9.88 +/- 0.21, average day-long glucose from 14.87 +/- 0.27 to 10.69 +/- 0.19 and HbAt1c(%) from 10.32 +/- 0.13 to 8.66 +/- 0.13. In the 2nd treatment group fasting glucose decreased from 14.59 +/- 0.61 to 9.05 +/- 37.28, average day-long glucose from 15.09 +/- 0.29 to 10.32 +/- 0.21 and HbA1c from 10.33 +/- 0.13 to 8.77+/-0.12 (for all P<0.0005). In this 2nd group, a decrease in LDL-cholesterol (P < 0.05) and an increase in HDL-cholesterol levels (P < 0.02) were also observed. In the 1st group, anthrombin III activity increased significantly (P<0.01). In the 2nd group, significant reductions in markers of platelet function (FP4 and betaTG, P < 0.01), thrombin generation (FPA, F1 + 2 and D-D, P<0.01), and fibrinolysis inhibition (PAI-1 activity, PAI-1 antigen, P< 0.001) were observed. Increases in some fibrinolytic activation markers (t-PA activity, and AT-III activity, P<0.01) occurred. Fasting lactate concentrations were unchanged in the metformin-treated group. No serious adverse effects were observed in either group. CONCLUSIONS: These results suggest that either high sulphonylurea dosages or a therapy combining lower sulphonylurea dosages with metformin are effective and safe in an aged but healthy population. Metformin provides additional benefits counteracting several cardiovascular risk factors but must be administered with caution, bearing in mind the general contra-indications for the drug but not age alone.     

2型糖尿病患者双胍类药物的临床应用调查

目的 观察糖尿病患者双胍类药物的使用情况.方法 对3 a来就诊的糖尿病患者进行登记,调查其用药情况.结果 有超过66%的病人在应用双胍类药物.在有缺氧性疾病的患者中的应用超过50%;并且仍有27%病人还在用降糖灵.结论 一定要强调双胍类药物的禁忌症,提倡合理用药,避免滥用.     

Rosiglitazone plus metformin is effective and well tolerated in clinical practice: results from large observational studies in people with type 2 diabetes

This study investigated the efficacy during daily practice of rosiglitazone (RSG) added to metformin (MET) in poorly controlled type 2 diabetes mellitus. Two post-marketing observational studies were conducted in Germany over 6 months. RSG (4 mg/day titrated to 8 mg/day as required) was added to existing MET in 11,014 subjects. Subjects were maintained on diet and exercise. Addition of RSG to MET significantly reduced median HbA 1c by 1.3% (8.1 vs. 6.8%; p < 0.0001) and median fasting blood glucose (FBG) by 47.0 mg/dl (171.0 vs. 124.0 mg/dl; p < 0.0001) after 6 months. The proportion of subjects achieving HbA(1c) targets of < or = 6.5 and < or = 7.0% increased from 3.5 to 38.8% and from 13.5 to 63.7%, respectively. Mean systolic and diastolic blood pressure decreased by 7 and 3 mmHg, respectively (p < 0.0001). Mean weight decreased by 1.7 kg and was constant or reduced in most (74.1%) subjects. Addition of RSG to MET significantly reduces median HbA 1c and FBG in clinical practice and is generally well tolerated.     

二甲双胍治疗多囊卵巢综合征肥胖型疗效观察

目的观察二甲双胍治疗多囊卵巢综合症 (PCOS) 肥胖型疗效. 方法将56例PCOS肥胖患者随机分为两组,分别用二甲双胍和克罗米芬治疗,并观察两组疗效以及治疗前后体重指数 (BMI)、胰岛素水平和葡萄糖耐量试验 (OGTT) 的变化. 结果治疗组妊娠率 (82%)明显高于对照组 (21%),在 BMI、胰岛素水平、OGTT改善方面两组比较,差异有显著性. 结论二甲双胍能明显改善PCOS的临床症状,提高妊娠率,改善肥胖,特别是对耐克罗米芬 PCOS有良好的治疗作用.     

高敏C反应蛋白在双胍类和磺脲类治疗后的糖尿病患者中的变化

目的探讨炎症因子高敏C反应蛋白(hs-CRP)在使用双胍类和磺脲类联合治疗12周后的2型糖尿病患者中的变化。方法采用免疫比浊法定量检测48例2型糖尿病患者治疗前后hs-CRP的水平,酶法检测空腹血糖(FBG)、血脂,高效液相法检测糖化血红蛋白(HbA1c),比较其治疗前后的变化。结果2型糖尿病患者治疗前后体质量指数(25.62±2.92)vs(25.09±2.98),腰围(85.73±8.66)cm vs(84.75±8.72)cm,FBG(7.92±1.43)mmol/L vs(5.96±1.31)mmol/L,总胆固醇(5.63±1.08)mmol/L vs(4.98±0.79)mmol/L,甘油三酯(2.19±2.09)mmol/L vs(1.58±0.96)mmol/L,低密度脂蛋白胆固醇(3.29±1.17)mmol/L vs(2.91±0.59)mmol/L,hs-CRP(1.66±0.93)mg/L vs(1.20±0.86)mg/L,HbA1c(7.29±1.26)%vs(6.79±0.96)%;上述指标治疗后较治疗前明显下降,其差异有统计学意义(均P<0.01)。结论2型糖尿病患者在血糖、体质量和腰围控制的同时hs-CRP水平降低,hs-CRP可作为临床医生治疗2型糖尿病及其血管并发症时疗效观察的监测指标之一。     

二甲双胍联合阿仑膦酸钠治疗骨质疏松症合并2型糖尿病的临床疗效

目的观察二甲双胍联合阿仑膦酸钠对骨质疏松症合并2型糖尿病的影响。方法将120例绝经后骨质疏松症合并2型糖尿病患者随机分为治疗组(n=60)和对照组(n=60)。对照组给予阿仑膦酸钠治疗,治疗组给予阿仑膦酸钠联合二甲双胍治疗,为期治疗6个月。检测治疗后两组患者髋部及腰椎骨密度和视觉模拟评分法(visual analogue scale,VAS)评分改变,同时测定血清骨代谢指标骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,B-ALP)和抗酒石酸酸性磷酸酶-5b(tartrate resistant acid phosphatase-5b,TRACP-5b)水平的变化,记录药物的不良反应。结果治疗前两组的骨密度、骨代谢指标和VAS评分比较没有统计学意义(P0.05)。治疗3个月和6个月后,两组髋部及腰椎密度都有不同程度的升高(P0.05),治疗组的骨密度提高较对照组更为显著(P0.05)。同时,各组血清B-ALP和TRACP-5b水平、VAS评分均降低(P0.05),治疗组的骨代谢指标和VAS评分改善较对照组更为显著(P0.05)。而两组之间的不良反应比较无明显差异(P0.05)。结论二甲双胍增加阿仑膦酸钠治疗骨质疏松症合并2型糖尿病临床疗效显著。