甘精胰岛素联合口服降糖药物对血糖控制不佳的2型糖尿病患者的疗效观察

目的 评价甘精胰岛素(来得时(R))与盐酸吡格列酮和二甲双胍联合应用治疗口服降糖药物控制不佳的2型糖尿病患者的有效性和安全性.方法 采用随机法将78例口服降糖药物控制不佳的2型糖尿病患者分为A、B两组.A组为甘精胰岛素(来得时(R))组,B组为精蛋白锌胰岛素(诺和灵N)组,两组均口服吡格列酮和二甲双胍,观察治疗后空腹血...     

甘精胰岛素联合口服降糖药物对血糖控制不佳的2型糖尿病患者的疗效观察

Objective To investigate the efficacy and safety of insulin glargine(lantus(R))combined with metformin and pioglitazone in type 2 diabetic patients whose blood glucose levels Were inadequately controlled by oral antidiabetic drugs(OAD).Methods 78 type 2 diabetic patients with poor glycemic control of OAD were randomly divided into group A and B.Patients in group A and B received insulin glargine and NPH insulin respectively in addition to OAD of metformin and pioglitazone.Fasting blood glucose(FBG),2-bour postprandial blood glucose(2 hVG),glycosylated hemoglobin(Hb)A1c and the increase of weight,as well as hypoglycemia rate were abserved after therapy.Results Levels of FBG,2 hPG and HbA1c were lower in group A than those in group B(P<0.05).In group A FBG is(5.17±0.96)mmol/L,2 hPG is (6.93±1.20)mmol/L,HbA1c is(5.27±0.81)%,while in group B FBG is(5.48±1.03)mmol/L,2 hPG is(7.33 ±1.09)mmol/L,HbA1c is(5.98 ±0.98)%.No difference could be found in hypoglycaemia between two groups(P>0.05).Conclusion The treatment of insulin glargine with metformin and piglitazone in type 2 diabetic patients with poor glycemic control is more efficient.As the basic insulin treatment,glarglne Was more efficient than NPH insulin.     

Efficacy and tolerability of vildagliptin in type 2 diabetic patients on hemodialysis

Anti‐diabetic agent‐related hypoglycemia is a serious complication in type 2 diabetic patients on hemodialysis. Therefore, we assessed the efficacy and tolerability of 24 weeks of monotherapy with vildagliptin, a dipeptidyl peptidase four inhibitor, which is a new class of antidiabetic agent. This open‐label, single‐arm clinical trial was performed on 26 patients on hemodialysis. The primary assessments were changes in postprandial glucose level and glycated albumin (GA). During the study, three patients dropped out, and data from 23 patients were analyzed. Significant reductions were seen in postprandial glucose (−2.60 ± 3.80 mmol/L, P < 0.001) and GA (−2.59 ± 2.33%, P < 0.001) levels. No serious drug‐related adverse events were observed. Vildagliptin monotherapy can be recommended for glycemic control in type 2 diabetic patients on hemodialysis. This trial was registered with the University Hospital Medical Information Network (no. UMIN000003661). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00169.x, 2011)     

Efficacy of liraglutide therapy in Japanese type 2 diabetic patients insufficiently controlled with basal‐supported oral therapy

(J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00223.x, 2012) Aims/Introduction: We assessed the efficacy of liraglutide therapy in Japanese type 2 diabetic patients insufficiently controlled with basal‐supported oral therapy (BOT). Materials and Methods: We retrospectively analyzed the data of 37 patients who had postprandial hyperglycemia (≥10.0 mmol/L) with BOT (long‐acting insulin plus glimepiride) with their insulin titrated enough to keep preprandial glycemia <7.2 mmol/L, and who had their treatment changed to liraglutide monotherapy, with the subsequent addition of glimepiride, when required. Those who achieved the glycemic target at all points (preprandial glycemia <7.2 mmol/L and postprandial glycemia <10.0 mmol/L) were regarded as responders and the efficacy of liraglutide therapy was assessed. We also explored the predictive clinical characteristics associated with its efficacy. Results: Daily doses of insulin and glimepiride with BOT were 14 ± 9 units and 1.5 ± 0.9 mg, respectively. After the change to liraglutide therapy, 37% of the patients appeared to be responders to the therapy, whereas 12% had their glycemic control rather deteriorated. Efficacy of liraglutide therapy was significantly associated with baseline insulin dosage and post‐breakfast glycemia with BOT. The C‐statistic of the model was calculated to be 0.90. Conclusions: There were responders and non‐responders to liraglutide therapy in Japanese BOT failures. It is likely that baseline insulin dosage and post‐breakfast glycemia with BOT are clinically useful indicators for the efficacy of liraglutide therapy.     

Serum C-peptide levels determine glycemic responses in type II diabetic patients treated with combined insulin and sulfonylurea agent

Type II diabetes mellitus is a heterogeneous disease. Selection of either insulin or a sulfonylurea agent in addition to diet is usually made empirically. In patients who fail to respond to either agent alone, the potential benefit of combined insulin and sulfonylurea therapy is unclear. We therefore evaluated nine poorly controlled insulin treated type II diabetic patients after addition of a sulfonylurea agent--glyburide--for four weeks. Glycosylated hemoglobin (HbA1c), serum glucose, and C-peptide responses to oral glucose were evaluated. Based on a reduction of at least 50 mg/dl in the fasting serum glucose (FSG) at the end of the first week of the combination therapy or a FSG of less than 140 mg/dl, two groups were arbitrarily identified: responders (n = 5) and nonresponders (n = 4). Clinical characteristics including mean age, weight, duration of diabetes, daily dose of insulin, and duration of insulin treatment were not statistically different between the two groups. Mean baseline FSG and HbA1c levels were also not statistically different in both groups. An improvement in mean FSG and glucose tolerance occurred in the responders at the end of four weeks of combined therapy (FSG: 291 +/- 25 vs. 189 +/- 6 mg/dl, p less than 0.05; HbA1c 10.76 +/- 0.80 vs. 9.40 +/- 0.21%, p = NS). The nonresponders had no change in glucose tolerance. The mean fasting and stimulated serum C-peptide levels were significantly higher in the responders at week 4 compared with that of the nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety of nateglinide plus vildagliptin combination therapy compared with switching to vildagliptin in type 2 diabetes patients inadequately controlled with nateglinide

Aims/Introduction

To investigate the efficacy and safety of vildagliptin, a potent dipeptidyl peptidase‐4 inhibitor, as add‐on to nateglinide, compared with switching to vildagliptin in Japanese type 2 diabetes patients poorly controlled with nateglinide.

Materials and Methods

A total of 40 patients inadequately controlled with nateglinide were randomized to the switching group (n = 20, switching from nateglinide to vildagliptin) or combination group (n = 20, nateglinide plus vildagliptin). A meal tolerance test was carried out at weeks 0 and 24.

Results

The mean changes in glycated hemoglobin from baseline to week 24 were −1.2 ± 0.3% and −0.3 ± 0.5% in patients of the combination and switching groups, respectively, and the difference between the groups was statistically significant (P < 0.001). The mean changes in area under the curve of glucose from 0 to 180 min (AUC_0–180 min) from baseline to week 24 was −361 ± 271.3 mmol·min/L in patients of the combination group compared with 141 ± 241.9 mmol·min/L in those of the switching group (P < 0.001). The incidence of hypoglycemic events was low (three in the combination group), and none of the patients developed severe hypoglycemia. Although the addition of vildagliptin to nateglinide did not significantly increase insulin secretion relative to glucose elevation (ISG) after meal load (ISG_0–180 min: AUC_0–180 min insulin / AUC_0–180 min glucose) in comparison with that in baseline, the mean ISG_0–30 min 24 weeks after addition of vildagliptin to nateglinide was significantly higher than that at baseline. In contrast, switching from nateglinide to vildagliptin reduced the mean ISG_0–180 min, relative to baseline.

Conclusions

The combination therapy of vildagliptin and nateglinide is effective and safe in Japanese type 2 diabetes, and the improved glycemic control is as a result of augmentation of nateglinide‐induced early phase insulin secretion. This trial was registered with UMIN (no. ID000004010).     

口服降糖药联合胰岛素治疗2型糖尿病磺酰脲类药物继发性失效的疗效

探讨316例口服降糖药联合中效胰岛素（NPH）治疗2型糖尿病磺酰脲类药物继发性失效的疗效。患者分成四组：A组为NPH＋二甲双胍（Met）＋阿卡波糖（Acar）组,B组为NPH＋Met组,C组为NPH＋Acar组,D组为NPH＋Met＋格列齐特（Glic）组,每组79例,记录治疗前后临床指标。结果显示D组控制空腹血糖最好,A组控制餐后血糖最佳。     

口服二甲双胍血糖控制不佳的2型糖尿病患者联合西格列汀治疗的有效性和安全性

目的评价口服二甲双胍血糖控制不佳的2型糖尿病患者联合西格列汀治疗的有效性与安全性。方法采用随机、开放、格列美脲平行对照的研究方法。102例口服二甲双胍控制不佳的2型糖尿病患者随机分为早餐前口服西格列汀100 mg（n=52）或早餐前口服格列美脲1~4 mg（n=50）两组,同时继续口服二甲双胍,进行为期24周的观察。结果①基线时两组口服二甲双胍的时间及其他指标相似;②24周时,西格列汀组与格列美脲组的平均HbA1c分别下降了1.41%和1.38%,日平均血糖降幅分别为5.28 mmol/L和4.56 mmol/L;③试验结束时,西格列汀组和格列美脲组分别有3.80%和10.00%的患者发生症状性低血糖（3次和18次）,其中严重低血糖事件,西格列汀组为0次,格列美脲组有4.00%患者（3次）,夜间低血糖西格列汀组为0次,格列美脲组有4.00%患者（2次）,两组间差异有统计学意义（均P〈0.05）;④试验结束时西格列汀组患者平均体重下降1.0 kg,格列美脲组平均增加1.2 kg,两组间差异有统计学意义（P〈0.01）。结论与格列美脲相比,西格列汀联合二甲双胍可使2型糖尿病患者的血糖得到有效控制,且低血糖发生率明显降低,体重下降;因此,作为控制2型糖尿病血糖的二线用药,西格列汀优于格列美脲。     

口服二甲双胍血糖控制不佳的2型糖尿病患者联合西格列汀治疗的有效性和安全性

目的 评价口服二甲双胍血糖控制不佳的2型糖尿病患者联合西格列汀治疗的有效性与安全性.方法 采用随机、开放、格列美脲平行对照的研究方法.102例口服二甲双胍控制不佳的2型糖尿病患者随机分为早餐前口服西格列汀100 mg(n=52)或早餐前口服格列美脲1～4 mg(n=50)两组,同时继续口服二甲双胍,进行为期24周的观察.结果 ①基线时两组口服二甲双胍的时间及其他指标相似;②24周时,西格列汀组与格列美脲组的平均HbA1c分别下降了1.41％和1.38％,日平均血糖降幅分别为5.28 mmol/L和4.56 mmol/L;③试验结束时,西格列汀组和格列美脲组分别有3.80％和10.00％的患者发生症状性低血糖(3次和18次),其中严重低血糖事件,西格列汀组为0次,格列美脲组有4.00％患者(3次),夜间低血糖西格列汀组为0次,格列美脲组有4.00％患者(2次),两组间差异有统计学意义(均P＜0.05);④试验结束时西格列汀组患者平均体重下降1.0 kg,格列美脲组平均增加1.2 kg,两组间差异有统计学意义(P＜0.01).结论 与格列美脲相比,西格列汀联合二甲双胍可使2型糖尿病患者的血糖得到有效控制,且低血糖发生率明显降低,体重下降;因此,作为控制2型糖尿病血糖的二线用药,西格列汀优于格列美脲.     

胰岛素联合维格列汀治疗2型糖尿病合并中度肾损伤患者的有效性和安全性

选取2012年12月至2013年11月于天津医科大学代谢病医院和天津滨海新区解放路社区卫生服务中心门诊或住院治疗的胰岛素治疗且血糖控制不佳的中度肾损伤的2型糖尿病（T2DM）患者143例,在现有胰岛素不变的基础上加用维格列汀50 mg每日1次口服治疗12周.比较治疗前后糖化血红蛋白（HbA1c）、空腹血糖（FPG）、预估肾小球滤过率（eGFR）、血红蛋白（Hb）和胰岛素用量变化情况,评估用药后的不良事件以及患者和医师的满意度.132例患者完成12周维格列汀药物治疗.与治疗前相比,治疗后HbA1c降低0.7％,FPG降低了1.8 mmol/L,胰岛素用量减少了8.0U,治疗前后差异具有统计学意义[分别为：（8.4±0.8）％比（7.7±1.2）％,=7.515;（10.6±2.6）比（8.8±1.4） mmol/L,t =9.476;（51 ±16）比（43±15） U/d,t=4.421;均P＜0.05];Hb和eGFR治疗前后无差异（均P ＞0.05）.治疗中无胰腺炎、死亡等严重不良事件的发生.医师对于中度肾损伤患者应用维格列汀治疗的满意度达94.7％,患者自身的满意度为94.0％.胰岛素联合维格列汀50 mg每日1次可改善中度肾损伤患者的血糖水平,同时具有良好的耐受性和安全性.     

Efficacy and tolerability of vildagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes mellitus

Aim: To investigate the efficacy and tolerability of vildagliptin as add‐on therapy to metformin in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. Methods: This was a 24‐week, randomized, double‐blind, placebo‐controlled study. Patients with T2DM (N = 438) with haemoglobin A1c (HbA1c) of 7.0–10.0% and fasting plasma glucose (FPG) <15 mmol/l (<270 mg/dl) were randomized (1 : 1 : 1) to vildagliptin 50 mg bid, vildagliptin 50 mg qd or placebo in addition to metformin. Results: The treatment groups were well balanced at baseline [mean HbA1c, 8.0%, FPG, 8.8 mmol/l (158 mg/dl); body mass index, 25.5 kg/m²]. The adjusted mean change (AMΔ) in HbA1c at endpoint was ?1.05 ± 0.08%, ?0.92 ± 0.08% and ?0.54 ± 0.08% in patients receiving vildagliptin 50 mg bid, 50 mg qd and placebo, respectively. The between‐treatment difference (vildagliptin 50 mg bid–placebo) was ?0.51 ± 0.11%, p < 0.001. A greater proportion of vildagliptin‐treated patients met at least one responder criterion (82.1 and 70.7%) compared to placebo‐treated patients (60.4%). The AMΔ at endpoint for FPG with vildagliptin 50 mg bid, ?0.95 mmol/l (?17.1 mg/dl); 50 mg qd, ?0.84 mmol/l (?15.1 mg/dl) was significantly different compared with the placebo ?0.26 mmol/l (?4.68 mg/dl) (p ≤ 0.001). Adverse events (AEs) were reported as 34.2, 36.5 and 37.5% for patients receiving vildagliptin 50 mg bid, 50 mg qd or placebo, respectively. Two patients in the vildagliptin 50 mg qd and one in the placebo group reported serious AEs, which were not considered to be related to the study drug; one incidence of hypoglycaemic event was reported in the vildagliptin 50 mg bid group. Conclusion: Vildagliptin as add‐on therapy to metformin improved glycaemic control and was well tolerated in Chinese patients who were inadequately controlled by metformin only.     

血糖波动与糖尿病周围神经病变的相关性

目的 探讨血糖波动与糖尿病周围神经病变（DPN）严重程度的相关性. 方法 选取DPN患者126例,根据多伦多神经病变评分分为轻、中、重度组.所有患者均采用动态血糖监测系统（CGMS）监测72 h,计算平均血糖水平（MBG）、日内平均血糖波动幅度（MAGE）、血糖波动最大幅度（DMMG）、血糖标准差（SD）,并记录年龄、性别、病程、BMI、HbA1c及一般生化指标. 结果 MBG、MAGE、SD随着神经病变严重程度的增加而增加（P＜0.05）,神经病变严重程度分别与MBG、MAGE呈正相关（β=0.249、0.196,P＜0.05）. 结论 T2DM患者血糖波动可能与DPN严重程度相关.     

2型糖尿病糖化血红蛋白与血糖波动关系分析

如何准确评价糖尿病的血糖控制状况成为当前的热门话题.糖化血红蛋白(HbA1c)是目前糖尿病筛选、血糖控制、疗效评估的有效检测指标,但其能否真实、全面地反映患者血糖控制情况呢?     

磺脲类降糖药继发性失效的2型糖尿病患者血浆胰淀素水平

在各30例的正常对照组，2型糖尿病患者磺脲类药物治疗有效组和继发性失效组进行口服75g葡萄糖耐量试验，测定各时间点血糖，胰岛素和胰淀素水平，结果提示高糖刺激的胰淀素分泌量的增加可能与2型糖尿病的发病和碘脲类降糖药继发性失效有关。     

甘精胰岛素与格列美脲联合应用治疗口服降糖药控制不佳2型糖尿病的有效性和安全性

目的 评价甘精胰岛素(来得时~(R))与格列美脲(亚莫利~(R))联合应用治疗口服降糖药控制不佳的2型糖尿病的有效性和安全性.方法 采用随机、开放、低精蛋白锌胰岛素注射液(诺和灵N)平行对照和多中心临床研究方法.122例口服降糖药控制不佳的2型糖尿病患者随机分为睡前注射一次甘精胰岛素(n=62)或低精蛋白胰岛素(n=60),清晨口服3mg格列美脲两组,进行为期24周的观察.结果 (1)基线时除甘精胰岛素组口服降糖药物使用的时间显著长于低精蛋白胰岛素组之外,两组其他指标相似;(2)24周时,甘精胰岛素组与低精蛋白胰岛素组的平均HbA_(1C)分别下降了1.38%和1.41%,平均空腹血糖分别从12.30和11.90 mmol/L降至6.05和6.19 mmol/L,日平均血糖降幅分别为5.28和4.56 mmol/L;(3)试验结束时,甘精胰岛素组和低精蛋白胰岛素组分别有46.8%和71.1%的患者发生症状性低血糖(156次和293次),其中严重低血糖事件分别为3.2%和15.0%(2次和21次),夜间低血糖分别为37.1%和61.7%(87次和229次),两组间差异均具有显著统计学意义(P<0.05或P<0.01);(4)甘精胰岛素组与低精蛋向胰岛素组的日平均胰岛素剂量分别从9.7 IU和9.8 IU增至32.5 IU和29.5 IU.结论 与低精蛋白胰岛素比较,睡前注射一次甘精胰岛素和清晨口服3 mg格列美脲联合应用可使口服降糖药控制不佳的2型糖尿病患者得到良好控制,且严重低血糖和夜间低血糖的发生率降低;作为基础胰岛素治疗,甘精胰岛素优于低精蛋白胰岛素.     

Efficacy of glimepiride in Japanese type 2 diabetic subjects

We investigated the efficacy of glimepiride, a third-generation sulfonylurea (SU), in Japanese type 2 diabetic patients in whom glycemic control had been inadequate with a conventional SU, gliclazide or glibenclamide. A total of 172 Japanese type 2 diabetic patients (HbA1C > or = 7.0%), maintained on a conventional SU, were randomly assigned to the 3rd SU group (SU treatments switched to glimepiride) or the 2nd SU group (treatments not changed). The conventional SU was switched to the indicated doses of glimepiride (gliclazide 40 mg = glimepiride 1 mg, glibenclamide 2.5 mg = glimepiride 2 mg). After 6 months, glycemic control (HbA1C and fasting plasma glucose) had not changed significantly in either the 2nd or the 3rd SU group. The homeostasis assessment model of insulin resistance (HOMA-IR) in the 3rd SU group was decreased by more than 10% (p = 0.015), whereas no change was observed in the 2nd SU group. The triglyceride level was decreased by approximately 10% in the 3rd SU group, not a significant change (p = 0.080). Patients who had been treated with only SU, or treated with SU for a short time (less than 5 years), and who were also obese (BMI > or = 25) or had a high HOMA-IR (HOMA-IR > or = 3), showed significantly reduced insulin resistance. According to logistic regression analysis, high BMI ( > or = 25) was the only variable predicting that glimepiride would more effectively improve HbA1C than conventional SU treatment. In conclusion, switching conventional SUs to glimepiride reduced insulin resistance without improving glycemic control. A notable finding of this study is that glimepiride was more beneficial in obese than in non-obese Japanese type 2 diabetic patients.