西格列汀联合二甲双胍治疗老年人 2 型糖尿病临床观察

〔摘 要〕 目的：探讨西格列汀联合二甲双胍治疗老年 2 型糖尿病（T2DM）患者的临床疗效。方法：选取解放军联勤 保障部队第 900 医院 2019 年 1 月至 2019 年 12 月期间收治的 160 例 T2DM 患者,随机分为观察组与对照组,各 80 例。对 照组选用二甲双胍进行治疗,观察组选用二甲双胍联合西格列汀进行治疗,比较两组患者空腹血糖（FPG）、餐后 2 h 血糖 （2h PG）、糖化血红蛋白（HbA1c）以及治疗安全性的差异。结果：治疗前两组患者的 FPG、2h PG、HbA1c 水平,差异 无统计学意义（P ＞ 0.05）。治疗后观察组患者的 FPG、2h PG、HbA1c 水平均低于对照组,差异具有统计学意义（P ＜ 0.05）; 观察组患者不良反应发生率为 7.5 %,与对照组的 11.3 % 比较,差异无统计学意义（P ＞ 0.05）。结论：西格列汀联合二甲 双胍治疗老年人 T2DM 整体效果显著,可促进血糖降低,且具有较高的治疗安全性。     

Dipeptidyl peptidase-4 as a new target of action for type 2 diabetes mellitus: a systematic review

Type 2 diabetes mellitus is a metabolic disease leading to microvascular and macrovascular complications including coronary artery disease and stroke. Management of diabetes has been challenging, particularly in the presence of the enormous prevalence of obesity. In recent years, various inhibitors of the enzyme dipeptidyl peptidase (DPP)-4 have been developed to treat diabetes. The enzyme DPP-4 cleaves incretins, which, among other functions, stimulate insulin and suppresses glucagon. Inhibition of this enzyme results in an increase in the half-life and the sustained physiologic action of incretins, leading to an improvement in hyperglycemia. One such agent, namely sitagliptin (MK-04,310), has been introduced into the United States market, and another agent, vildagliptin (LAF237), is being used in Europe and elsewhere. This article is intended to evaluate the effectiveness of DPP-4 inhibitors as a therapeutic modality for managing type 2 diabetes. The authors conducted a literature search of various databases to identify the clinical trials involving the DPP inhibitors and concluded that the DPP-4 inhibitors, for example, sitagliptin and vildagliptin, are efficacious for managing diabetes as monotherapy or combination therapy.     

Determination of sitagliptin in human urine and hemodialysate using turbulent flow online extraction and tandem mass spectrometry

High turbulence liquid chromatography (HTLC, or turbulent flow online extraction) and tandem mass spectrometry (MS/MS) methods for the determination of sitagliptin in human urine and hemodialysate were developed and validated to support clinical studies. A narrow bore large particle size reversed-phase column (Cyclone, 50 mm x 1.0 mm, 60 microm) and a BDS Hypersil C18 column (30 mm x 2.1 mm, 3 microm) were used as extraction and analytical columns, respectively. For the urine assay, the LLOQ was 0.1 microg/ml, the linear calibration range was 0.1 to 50 microg/ml, the interday precision (R.S.D.%, n=5) was 2.3-6.5%, and the accuracy was 96.9-106% of the nominal value. For the urine quality control samples (QCs), the intraday precision (R.S.D.%, n=5) and accuracy were 1.8-2.6% and 96.2-106% of the nominal value, respectively. The interday precision (R.S.D.%) for 56 sets of urine QCs over a 6-month period varied from 3.8% to 5.5% and the accuracy from 102% to 105% of the nominal value. For the hemodialysate assay, the LLOQ was 0.01 ng/ml, the linear dynamic range was 0.01-5.0 ng/ml, the interday precision was 1.6-4.1%, and the accuracy was 89.8-104% of the nominal value. For hemodialysate QCs, the intraday precision and accuracy varied from 2.3% to 8.9% and from 99.8% to 111% of the nominal value, respectively. These results demonstrated that both methods are selective, accurate, precise, reproducible, and suitable for quantifying sitagliptin in hemodialysate and human urine samples.     

磷酸西格列汀联合二甲双胍治疗初发2型糖尿病的应用效果与价值

目的 分析磷酸西格列汀联合二甲双胍治疗初发2型糖尿病的应用效果与价值.方法 104例初治2型糖尿病患者,按照随机盲选法分成观察组和对照组,每组52例.对照组实行常规治疗,观察组实行磷酸西格列汀联合二甲双胍治疗.比较两组临床疗效、低血糖发生率以及治疗前后血糖水平、胰岛素指标、体质量指数.结果 观察组治疗总有效率高于对照组...     

Differential Effects of DPP-4 Inhibitors,Anagliptin and Sitagliptin,on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. We investigated PCSK9 concentration in type 2 diabetes mellitus (T2DM) and the impact of treatment with anagliptin or sitagliptin on PCSK9 level as a sub-analysis of the REASON trial. Methods: PCSK9 concentration was measured at baseline and after 52 weeks of treatment with anagliptin ( n =122) or sitagliptin ( n =128) in patients with T2DM who were receiving statin therapy. All of the included patients had been treated with a DPP-4 inhibitor prior to randomization. Results: Baseline PCSK9 level was positively, but not significantly, correlated with LDL-C and was independently associated with platelet count and level of triglycerides. Concomitant with reduction of LDL-C, but not hemoglobin A1c (HbA1c), by anagliptin, PCSK9 level was significantly increased by treatment with sitagliptin (218±98 vs. 242±115 ng/mL, P =0.01), but not anagliptin (233±97 vs. 250±106 ng/mL, P =0.07). Conclusions: PCSK9 level is independently associated with platelet count and level of triglycerides, but not LDL-C, in patients with T2DM. Anagliptin reduces LDL-C level independent of HbA1c control in patients with T2DM who are on statin therapy possibly by suppressing excess statin-mediated PCSK9 induction and subsequent degradation of the LDL receptor.     

西格列汀或瑞格列奈联合甘精胰岛素治疗2型糖尿病的临床观察

目的比较西格列汀联合甘精胰岛素与瑞格列奈联合甘精胰岛素治疗2型糖尿病（T2DM）的疗效。方法将2011年1月-2012年12月80例服用2种口服降糖药（OAD）血糖控制不佳的T2DM患者,按就诊奇偶顺序分为观察组和对照组各40例,观察组采用西格列汀联合甘精胰岛素予以治疗,对照组应用瑞格列奈联合甘精胰岛素治疗,治疗12周,观察两组患者空腹血糖（FBG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）、体质量指数（BMI）等指标及胰岛素用量、低血糖发生情况。结果治疗后两组FBG、2hPG、HbA1c均较前下降（P〈0.05）;观察组与对照组HbA1c达标率分别为88.3%、87.8%,但观察组胰岛素用量比对照组减少12.1%,且BMI得到控制,低血糖发生率低。结论西格列汀联合甘精胰岛素治疗可有效控制血糖和体质量,减少低血糖事件,在同等HbA1c达标率下,所用的胰岛素剂量更少。     

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus

Aims/hypothesis The aim of this study was to assess the efficacy and safety of sitagliptin (MK-0431) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA_1c ≥7% and ≤10%) on exercise and diet.Methods A total of 521 patients aged 27–76 years with a mean baseline HbA_1c of 8.1% were randomised in a 1:2:2 ratio to treatment with placebo, sitagliptin 100 mg once daily, or sitagliptin 200 mg once daily, for 18 weeks. The efficacy analysis was based on an all-patients-treated population using an analysis of covariance, excluding data obtained after glycaemic rescue.Results After 18 weeks, HbA_1c was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo (placebo-subtracted HbA_1c reduction: −0.60% and −0.48%, respectively). Sitagliptin also significantly decreased fasting plasma glucose relative to placebo. Patients with higher baseline HbA_1c (≥9%) experienced greater placebo-subtracted HbA_1c reductions with sitagliptin (−1.20% for 100 mg and −1.04% for 200 mg) than those with HbA_1c <8% (−0.44% and −0.33%, respectively) or ≥8% to 8.9% (−0.61% and −0.39%, respectively). Homeostasis model assessment beta cell function index and fasting proinsulin:insulin ratio, markers of insulin secretion and beta cell function, were significantly improved with sitagliptin. The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo. Sitagliptin had a neutral effect on body weight.Conclusions/interpretation Sitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.For the Sitagliptin Study 023 Group see electronic supplementary material for list of study investigators.     

西格列汀联合津力达颗粒治疗老年2型糖尿病疗效及安全性

目的 探讨西格列汀联合津力达颗粒治疗老年2型糖尿病的疗效和安全性。方法 选取我院2019年5月至2020年1月期间收治的90例老年2型糖尿病患者为研究对象,按随机数字表法分为对照组和观察组,各45例。对照组患者给予口服西格列汀片治疗,100 mg/次,1次/d,观察组患者在对照组治疗方案的基础上联用津力达颗粒治疗,9g/次,3次/d。统计两组患者治疗效果、血糖指标和胰岛功能指标变化以及不良反应发生情况。结果 观察组临床总有效率为93.3%,显著高于对照组;两组患者血糖指标和胰岛功能指标均显著改善,但观察组水平显著优于对照组;观察组总不良反应发生率为8.9%,显著低于对照组,差异均具有统计学意义(P<0.05)。结论 西格列汀联合津力达颗粒治疗老年2型糖尿病,作用机制互补,疗效确切,安全性高,值得临床推广。     

西格列汀上市后致皮肤不良反应的信号挖掘与评价

目的:挖掘与评价西格列汀皮肤不良反应的信号,为临床用药提供参考。方法:采用报告比值比(ROR)法对美国不良事件报告系统(AERS)进行信号挖掘,找出西格列汀皮肤不良反应的相关信号,利用SPSS16.0分析年龄、性别、用药时间、剂量对信号的影响。结果:纳入2009-2011年AERS的数据共挖掘出西格列汀165个可疑的不良反应信号,其中皮肤不良反应信号24个。通过统计学分析发现皮肤不良反应相对于其他不良反应,在性别(P=0.341)、年龄(P=0.229)、用药时间(P=0.078)、用药剂量(P=0.226)中的分布差异均无统计学意义。结论:挖掘和评价AERS数据库得到西格列汀皮肤不良反应的信号及影响因素,为其在临床使用提供依据,为进一步的药物警戒工作奠定基础。