Comparison of the efficacy of sitagliptin and glimepiride dose‐up in Japanese patients with type 2 diabetes poorly controlled by sitagliptin and glimepiride in combination

Aims/Introduction

The goal of the study was to examine the effects of sitagliptin dose‐up or glimepiride dose‐up in Japanese patients with type 2 diabetes who were controlled inadequately by sitagliptin and glimepiride in combination.

Materials and Methods

A multicenter, prospective, randomized, open‐label study was carried out in 50 patients with type 2 diabetes treated with sitagliptin and low‐dose glimepiride. The patients were randomly assigned to receive the addition of 50 mg/day sitagliptin or 0.5 mg/day glimepiride. The primary end‐point was the percentage change in glycated hemoglobin (HbA1c).

Results

During a follow‐up period, the difference in the percentage changes in HbA1c between the two groups was not significant (P = 0.13). However, HbA1c was significantly decreased by glimepiride dose‐up (P < 0.01 vs baseline), but not by sitagliptin dose‐up (P = 0.74). Univariate linear regression analyses showed that the percentage change in HbA1c was significantly associated with the serum level of arachidonic acid (AA) in both groups.

Conclusions

There was no significant difference in the HbA1c‐lowering effects between the two groups. However, a significant HbA1c‐lowering effect from baseline of glimepiride dose‐up was found, and the AA level showed a negative correlation with the decrease in HbA1c in the sitagliptin dose‐up group, but a positive correlation in the glimepiride dose‐up group. These findings suggest that the AA level is associated with HbA1c reduction in response to dose‐up with these drugs in patients with type 2 diabetes in a combination therapy with sitagliptin and glimepiride. This trial was registered with UMIN (no. 000009544).     

Efficacy of glimepiride/metformin fixed‐dose combination vs metformin uptitration in type 2 diabetic patients inadequately controlled on low‐dose metformin monotherapy: A randomized,open label,parallel group,multicenter study in Korea

Aims/Introduction

To compare the efficacy and safety of early combination therapy with glimepiride/metformin to metformin uptitration in reducing glycated hemoglobin (HbA1c) levels in Korean type 2 diabetic patients inadequately controlled on low-dose metformin monotherapy.

Materials and Methods

In a randomized, open label, parallel group, multicenter study, 209 Korean type 2 diabetic patients (HbA1c 7.0–10.0%, on metformin 500–1,000 mg/day) received glimepiride/metformin fixed-dose combination (G/M FDC) or metformin uptitration treatment (Met UP). The primary end-point was the change in HbA1c from baseline to week 24.

Results

G/M FDC therapy provided significantly greater adjusted mean decreases vs Met UP therapy in HbA1c (−1.2 vs −0.8%, P < 0.0001), and fasting plasma glucose (−35.7 vs −18.6 mg/dL, P < 0.0001). A significantly greater proportion of patients with G/M FDC therapy achieved HbA1c < 7% (74.7 vs 46.6%, P < 0.0001) at the end of the study. More patients experienced hypoglycemia with G/M FDC therapy compared with Met UP therapy (41 vs 5.6%, P < 0.0001), but there was no serious hypoglycemia in any group. A modest increase in mean bodyweight occurred in the patients who were treated with G/M FDC therapy (1.0 kg), whereas a slight decrease was observed in the patients who were treated with Met UP therapy (−0.7 kg).

Conclusion

The present study showed that glimepiride/metformin fixed-dose combination therapy was more effective in glycemic control than metformin uptitration, and was well tolerated in type 2 diabetic patients inadequately controlled by low-dose metformin monotherapy in Korea. This trial was registered with ClinicalTrial.gov (no. {"type":"clinical-trial","attrs":{"text":"NCT00612144","term_id":"NCT00612144"}}NCT00612144).     

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。     

LC-UV-PDA and LC-MS studies to characterize degradation products of glimepiride

Degradation products of glimepiride formed under different forced conditions have been characterized through LC-UV-PDA and LC-MS studies. Glimepiride was subjected to forced decomposition under the conditions of hydrolysis, oxidation, dry heat and photolysis, in accordance with the ICH guideline Q1A(R2). The reaction solutions were chromatographed on reversed phase C8 (150 mm x 4.6mm i.d., 5 microm) analytical column. In total, five degradation products (I-V) were formed under various conditions. The drug degraded to products II and V under acid and neutral hydrolytic conditions while products I, III and IV were formed under the alkaline conditions. The products II and V were also observed on exposure of drug to peroxide. No additional degradation product was shown up under photolytic conditions. All the products, except I, could be characterized through LC-PDA analyses and study of MS fragmentation pattern in both +ESI and -ESI modes. Product I could not be identified, as it did not ionize under MS conditions. The products II, III and V matched, respectively, to impurity B (glimepiride sulfonamide), impurity J and impurity C (glimepiride urethane) listed in European Pharmacopoeia. The product IV was a new degradation product, characterized as [[4-[2-(N-carbamoyl)aminoethyl]phenyl]sulfonyl]-3-trans-(4-methylcyclohexyl) urea. The degradation pathway of the drug to products II-V is proposed, which is yet unreported.     

格列美脲治疗糖尿病伴代谢综合征患者的临床观察

目的研究格列美脲对糖尿病伴代谢综合征(MS)患者的治疗效果,并探讨其对胰岛素分泌功能和胰岛素敏感性的影响。方法对65例MS并存在糖尿病的患者给予格列美脲片1~8 mg/d,治疗12周,治疗前后测定空腹血糖(FPG),餐后2 h血糖(2hPG),空腹胰岛素(FIns)、餐后胰岛素(PIns)、糖化血红蛋白(HbA1c),计算胰岛素抵抗指数(HOMA-IR)。并观察治疗前后血压、血脂及体重的变化。结果治疗12周后,FPG、2hPG和HbA1c降低(P<0.01),FIns无明显改变(P>0.05),PIns增加(P<0.01);HOMA-IR较治疗前明显降低(P<0.01);治疗后体重指数、血压有轻微下降,但无统计学差异(P>0.05),总甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)较治疗前有所改善(P<0.05)。结论格列美脲能有效改善MS中糖尿病患者的糖代谢状态,既能刺激PIns分泌,又能明显改善胰岛素的敏感性,且对MS的其它代谢异常无不良影响。     

格列美脲联用甘精胰岛素或中性鱼精蛋白锌胰岛素治疗2型糖尿病的疗效及安全性

目的探讨格列美脲联用甘精胰岛素治疗磺脲类药物继发性失效的2型糖尿病患者的疗效及安全性。方法50例口服降糖药血糖控制不理想的2型糖尿病患者随机分为甘精胰岛素治疗组（IG组）和鱼精蛋白锌胰岛素治疗组（NPH组），予睡前皮下注射胰岛素联合口服格列美脲治疗12周，比较两组疗效及安全性。结果治疗后两组FBG、2hBG、HbA1c均明显下降，但IG组低血糖事件明显少于NPH组（P〈0．01）。结论格列美脲联用甘精胰岛素治疗2型糖尿病的方案安全有效，能减少低血糖事件的发生。     

地特胰岛素联合格列美脲治疗2型糖尿病的观察

目的观察地特胰岛素联合格列美脲治疗2型糖尿病的疗效。方法 60例2型糖尿病患者随机分为两组,A组为地特胰岛素联合格列美脲组,B组为生物合成人胰岛素注射液(NPH)联合格列美脲组。观察两组患者空腹血糖、(FBG)餐后2 h血糖(2hBG)、糖化血红蛋白(HbA1c)、胰岛素用量、低血糖发生率。结果两组治疗后,FBG、2hBG、HbA1c水平均较治疗前明显下降(P<0.05),二者间比较无统计学意义(P>0.05)。A组胰岛素用量、低血糖发生率明显低于B组(P<0.05)。结论地特胰岛素联合格列美脲降糖效果好,低血糖发生率低,安全方便。     

甘精胰岛素和格列美脲对初诊2型糖尿病的疗效对比研究

目的 对比甘精胰岛素与格列美脲治疗初诊2型糖尿病患者的临床疗效.方法 选取2011年1月-2012年1月我院收治的68例2型糖尿病患者,将患者按照使用治疗药物的不同分为观察组和治疗组.观察组采用甘精胰岛素联合二甲双胍治疗;对照组采用格列美脲联合联合二甲双胍治疗.比较两组患者治疗前后的B细胞功能情况、血糖控制情况、低血糖和体质指数情况.结果 治疗后两组患者的FPG、2hPG、HbA1c均较治疗前降低,差异有统计学意义（P＜0.01）;两组患者胰岛素分泌指数（HOMA-β）和胰岛素抵抗指数（HOMA-IR）差值比较,差异无统计学意义（P＞0.05）.观察组达标时间较对照组达标时间短,差异有统计学意义（P＜0.05）.结论 甘精胰岛素与格列美脲均能够对初诊2型糖尿病患者起到良好的治疗效果,但是甘精胰岛素在降糖方面更加迅速、客观.     

格列美脲对比格列本脲治疗2型糖尿病疗效和安全性的系统评价

目的:系统评价格列美脲对比格列本脲治疗2型糖尿病的疗效与安全性,以为临床提供循证参考。方法:计算机检索PubMed、The Cochrane library、Medline、EMBase、中国期刊全文数据库、万方数据库、维普数据库,纳入格列美脲对比格列本脲治疗2型糖尿病的随机对照试验(RCT),按Cochrane系统评价的方法评价纳入研究的质量,对结果采用Rev Man 5.2统计软件进行Meta分析。结果:共纳入14项RCT,合计3 398例患者。Meta分析结果显示,试验组在降低患者糖化血红蛋白[MD=0.08,95%CI(-0.18,0.02),P=0.13]、餐后血糖[MD=0.07,95%CI(-0.09,0.22),P=0.40]、总胆固醇[MD=-0.19,95%CI(-0.46,0.08),P=0.16]、甘油三酯[MD=-0.26,95%CI(-0.55,0.02),P=0.07]、低密度脂蛋白[MD=-0.10,95%CI(-0.22,0.01),P=0.08]方面与对照组比较差异无统计学意义;在降低空腹血糖[MD=-0.08,95%CI(-0.15,-0.01),P=0.03]、空腹胰岛素[MD=-0.82,95%CI(-1.13,-0.50),P<0.000]、餐后胰岛素[MD=-5.63,95%CI(-7.71,-3.55),P<0.000]、体质量指数[MD=-1.53,95%CI(-2.95,-0.12),P=0.03]、低血糖发生率[RR=0.45,95%CI(0.30,0.68),P<0.000]和改善高密度脂蛋白[MD=0.04,95%CI(0.00,0.07),P=0.04]等方面,与对照组比较差异有统计学意义。结论:与格列本脲相比,格列美脲可以显著改善2型糖尿病患者空腹血糖、体质量指数、高密度脂蛋白、空腹胰岛素、餐后胰岛素水平,且低血糖发生率较低。受纳入研究数量较少和质量的限制,尚需开展设计严谨的长期随访的大样本RCT,以为临床提供更多科学证据。     

格列美脲与利拉鲁肽治疗初诊2型糖尿病疗效对比研究

目的 对比利拉鲁肽与格列美脲治疗初诊2型糖尿病疗效及安全性。方法 门诊初诊2型糖尿病患者84例,随机分配为观察组与对照组,每组42例,对照组给予格列美脲联合二甲双胍治疗,观察组给予利拉鲁肽联合二甲双胍治疗,治疗12周,观察两组糖化血红蛋白（lycated hemoglobin Alc,HbA1c）、空腹血糖（Fasting plasma glucose,FPG）、餐后2h血糖（2-hour post-prandial plasma glucose,PBG）、胰岛素敏感指数（insulin sensitivity index,ISI）、体重及低血糖发生率,比较两组患者治疗的临床疗效。结果 两组治疗后HbA1c、FPG、PBG均明显下降（P〈0.01）,但两组下降差异无统计学意义（P〉0.05）;两组治疗前后ISI均有改善（P〈0.01）,观察组优于对照组（P〈0.01）;观察组体重下降明显（P〈0.01）,对照组体重稍增加（P〉0.05）;低血糖发生率对照组高于观察组;观察组出现5例一过性的恶心不良反应,对照组出现0例。结论 利拉鲁肽治疗2型糖尿病与格列美脲疗效相当,但具有减轻体重及低血糖发生率的优势。