利司鲁肽治疗2型糖尿病的系统评价

目的：系统评价新型GLP-1受体激动剂利司鲁肽治疗2型糖尿病的疗效与安全性。方法：电子检索中英文数据库中有关利司鲁肽治疗2型糖尿病的随机临床试验（RCT）,时限至2016年5月;2位研究者独立评阅文献,并筛选及予以质量评价;采用RevMan 5.0软件对各效应指标进行Meta分析。结果：纳入7篇RCT,文献质量评价均属低偏倚风险,2型糖尿病患者共计2 089例,其中试验组（利司鲁肽治疗）1 128例,对照组（安慰剂）961例,Meta分析结果显示,于治疗周期末,2组HbA_1c水平、HbA_1c达标率（≤6.5%）有统计学差异（P<0.05）,FPG水平变化无统计学差异（P>0.05）,恶心、呕吐、胃肠功能紊乱、低血糖反应及因不良事件（AE）退出治疗的发生率有统计学差异（P<0.05）,腹泻、头痛、头晕、鼻咽炎及SAE发生率无统计学差异（P>0.05）。结论：利司鲁肽对2型糖尿病患者血糖水平有较好控制作用,但其不良反应发生率仍有较大差异,尚需更多大样本、多中心随机临床试验予以证实。     

早发2型糖尿病患者的临床分析

目的:探讨早发2型糖尿病(T2DM)患者的临床特点.方法:将我院临床诊断为2型糖尿病的患者297例根据诊断年龄不同分为早发组101例(年龄≤40岁)和迟发组196例(年龄>40岁).对两组的BMI、肥胖率、HbA1C、FC-P、TG、HDI-C、FPG、P2hPG、TC、LDL-C、高血压率、收缩压及舒张压、糖尿病家族史阳性率、母亲糖尿病史阳性率、父亲糖尿病史阳性率进行对比.结果:两组的BMI、肥胖患者、高血压患者、HbA1C、FC-P、TG、HDI-C、糖尿病家族史阳性率、母亲糖尿病史阳性率相比差异均有显著性(P<0.05)或0.01);两组的FPG、P2hPG、TC、LDL-C、收缩压及舒张压、父亲糖尿病史阳性率相比差异无显著性(P>0.05).结论:早发T2DM患者存在严重的代谢紊乱,具有显著的家族性倾向.     

2型糖尿病的药物治疗

2型糖尿病的治疗已取得巨大进展。随着人们对2型糖尿病机制的不断探索,针对不同机制的新药层出不穷,最大限度地满足着患者的需求。笔者简述了当前2型糖尿病治疗药物的发展史,重点描述当前以胰高血糖素样肽-1(glucagon-likepeptide1,GLP-1)受体激动剂,DPP-4抑制剂和钠葡萄糖共转运蛋白-2(SGLT-2)抑制剂为代表的新型降糖药物的发现和研究热点。     

Linagliptin for the treatment of type 2 diabetes

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic agents that have been rapidly adopted since their introduction in 2006. There are now five agents in global use, with three approved for treatment of patients with type 2 diabetes (T2D) in the USA. The results of Phase III clinical trials for linagliptin, a new addition to this class of inhibitors (approved by the FDA on 2 May 2011), have now been published. We reported on a 24-week Phase III trial of linagliptin administered as monotherapy in patients with T2D. This agent is characterized by a pharmacokinetic and metabolic profile that may have important implications for the choice of treatment in certain patient populations.     

2型糖尿病住院患者心理健康状况及影响因素分析

目的探讨2型糖尿病住院患者的心理健康状况影响因素,为改善糖尿病患者心理健康状况提供参考依据。方法采用社会支持量表（SSRS）、焦虑自评量表（SAS）、抑郁自评量表（SDS）,随机抽取安徽省某三甲医院的243例住院糖尿病患者进行调查。采用t检验、单因素方差分析和Logistic回归分析对影响住院患者心理健康的因素进行分析。结果 2型糖尿病住院患者焦虑和抑郁的发生率分别为32.9%和52.7%。t检验和单因素方差分析结果显示：吸烟、性别和并发症是影响患者焦虑抑郁情况的因素。经多因素logistic逐步回归分析结果显示：月经济收入较低者、有并发症者和病程较长者容易出现焦虑情绪,有并发症和文化程度较低者社会支持程度较差。结论住院糖尿病患者心理状况较差,存在较严重的焦虑和抑郁情况。在治疗同时应注意健康教育和心理关怀,尤其是伴有并发症、病程较长和低收入的患者。对于已经出现心理疾病的病人进行及时的心理治疗,以全面提高病人康复水平。     

西格列汀联合二甲双胍治疗2型糖尿病的系统评价

目的 系统评价西格列汀( SITA)联合二甲双胍(MET)治疗2型糖尿病(T2DM)的疗效及安全性.方法 计算机检索Cochrane图书馆、PubMed( 1996.01～2011.12)、EMbase( 1996.01～2011.12)、http:\\www.clinicaltirals.gov,中国知网(1996.01～2011.12)、万方数据库(1998.01～2011.12),收集以西格列汀联合二甲双胍( SITA/MET)治疗T2DM的随机对照试验(RCT),由2位研究者根据纳入与排除标准筛选试验、提取试验资料并进行质量评价,用RevMan 5.1软件进行统计学分析.结果 共纳入5个RCT,合计2 831例患者.Meta分析结果显示:SITA/MET组较MET联合噻唑烷二酮类(thiazolidinediones,TZDs)及MET联合磺脲类(sulphonylureas,SU),在降低糖化血红蛋白水平方面差异无统计学意义(P=0.61和P=0.07),SITA/MET组较MET/SU组,低血糖发生率低[RR=0.22,95％CI(0.11,0.45),P＜0.000 l],相对于MET/SU组和MET/TZDs组使患者体重增加,SITA/MET组可使患者体重下降.结论 SITA/MET是治疗2型糖尿病的安全有效的药物,与MET/TZDs及MET/SU比较,具有同等降低糖化血红蛋白的疗效,同时可以降低患者的体重.SITA/MET较MET/SU组低血糖的发生率低.     

Empagliflozin for the treatment of type 2 diabetes

Introduction: Despite the availability of numerous anti-diabetes drugs and treatment guidelines, many patients with type 2 diabetes mellitus (T2DM) do not reach recommended targets for glycemic control. There remains an unmet need for effective and well-tolerated anti-diabetes agents that can be used as monotherapy or in combination with other therapies to improve glycemic control in patients with T2DM. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of treatment for T2DM that reduce hyperglycemia by reducing renal glucose reabsorption and thereby increasing urinary glucose excretion.

Areas covered: This paper reviews the pharmacokinetic and pharmacodynamic properties of the SGLT2 inhibitor empagliflozin, the results of clinical trials investigating the efficacy of empagliflozin given as monotherapy or as add-on therapy on glycemic control, body weight, and blood pressure in patients with T2DM, and the safety and tolerability profile of empagliflozin.

Expert opinion: Empagliflozin offers good glycemic efficacy, weight loss, blood pressure reduction, and a low risk of hypoglycemia. These attributes, coupled with the ability to be used in virtually any combination with other anti-diabetes agents and at any stage in the disease process, provide a welcome new agent to our armamentarium of drugs to help manage T2DM.     

利拉列汀治疗2型糖尿病的系统评价

目的:系统评价利拉列汀治2型糖尿病疗效及安全性。方法:检索Cochrane图书馆,PubMed,EMBASE,CBM,VIP,CNKI数据库。根据Cochrane手册对纳入的随机对照试验(RCT)进行质量评价,并用RevMan5.0软件进行Meta分析。结果:共纳入3个研究,Meta分析结果显示:在降低患者糖化血红蛋白(HbA1c)水平方面利拉列汀的疗效明显优于安慰剂组,且差异具有统计学意义[MD=-0.67,95%CI(-0.77,-0.57),P<0.01];利拉列汀在降低2型糖尿病患者空腹血糖方面的疗效明显优于安慰剂组,且差异具有统计学意义[MD=-1.25,95%CI(-1.56,-0.94),P<0.01];利拉列汀的不良反应发生率与安慰剂组相似,2组差异无统计学意义[OR=0.87,95%CI(0.69,1.10),P=0.24]。结论:系统评价结果显示,利拉列汀能有效治疗2型糖尿病,但其远期疗效及安全性有待进一步研究探讨。     

Cost-effectiveness analysis of dapagliflozin versus glimepiride as monotherapy in a Chinese population with type 2 diabetes mellitus

Objective: To evaluate the long-term cost-effectiveness of dapagliflozin (a novel sodium–glucose co-transporter-2 inhibitor) versus glimepiride (a widely used sulfonylurea), when applied as monotherapy in patients with type 2 diabetes mellitus (T2DM) in China.

Methods: Literature screening, meta-analysis and indirect comparison were used to compare efficacy and safety between dapagliflozin and glimepiride. Direct medication costs and medical expenditure on treating diabetes related comorbidities were calculated based on published and local sources and reported in 2015 Chinese Renminbi (RMB). A discount rate of 3% was applied to both costs and health effects. The Cardiff model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes, was used to generate outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs and quality-adjusted life years (QALYs) over a time horizon of 40 years from the health provider perspective. Univariate and probabilistic sensitivity analyses were performed to assess uncertainty in the model results.

Results: Compared with glimepiride, patients on dapagliflozin gained 1.01 QALYs, at a cost saving of RMB 49,065 in our simulated cohort. This resulted in a cost saving of RMB 48,585 per QALY gained with dapagliflozin. The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis (PSA).

Conclusions: Compared with glimepiride, dapagliflozin as monotherapy for T2DM is a more cost-effective treatment for T2DM patients on monotherapy in China. The weight control has been identified as the major contributor for the higher cost-effectiveness of dapagliflozin.     

Systematic review of the cost-effectiveness of biphasic insulin aspart 30 in type 2 diabetes

Abstract

Objectives:

To review the cost-effectiveness of biphasic insulin aspart (BIAsp 30) compared to other insulin regimens in the treatment of type 2 diabetes based on published literature.     

Sotagliflozin as a potential treatment for type 2 diabetes mellitus

Introduction: SGLT1 is the primary transporter responsible for the absorption of glucose and galactose in the intestine, while SGLT2 and SGLT1 are both involved in the renal reabsorption of glucose. SGLT2 inhibitors are a new class of oral antidiabetic drugs, acting by increasing urinary glucose excretion (UGE). They offer the advantages of a reduced risk of hypoglycaemia, a decrease in body weight and blood pressure and an efficacy at all stages of type 2 diabetes (T2DM).

Areas covered: Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor. Original publications in English were selected as the basis of this review. Clinical trials were identified using the Clinicaltrial.gov database.

Expert opinion: By a potential additional mechanism of action on intestinal glucose absorption linked to SGLT1 inhibition, sotagliflozin differentiates from SGLT2 inhibitors by reducing postprandial glucose excursion and insulin secretion, as well as by increasing GLP-1 secretion. Despite a weaker effect on UGE than selective SGLT2 inhibitors, sotagliflozin is as effective as SGLT2 inhibitors on HbA1C reduction, with a similar safety profile in short-term studies. While sotagliflozin was first assessed in T2DM, it is now in phase 3 development as an adjuvant treatment in patients with T1DM after positive results from a pilot study.     

Luseogliflozin for the treatment of type 2 diabetes

Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are expected to provide adequate glycemic control, and be safe and well tolerated, for treating type 2 diabetes mellitus (T2DM). Luseogliflozin is a highly selective SGLT2 inhibitor that was recently approved for marketing and launched in Japan to treat T2DM.

Areas covered: This review summarizes the published data regarding the mechanism of action, clinical efficacy, and safety of luseogliflozin for treating T2DM. Other potential benefits of luseogliflozin, including lowering body weight and blood pressure, beyond its glucose-lowering effects are also discussed.

Expert opinion: Luseogliflozin lowers plasma glucose concentration and body weight, and has beneficial effects on other clinically relevant parameters, including blood pressure and uric acid, in patients with T2DM. Although it had a good safety profile in clinical trials, there may be some safety concerns, including a possible decrease in muscle mass and an increase in ketone bodies. Therefore, careful administration and consideration of its benefit–risk balance are necessary. When using luseogliflozin, it is important to select appropriate patients and to adhere to its guidelines for use. If used correctly, luseogliflozin is expected to be positioned as a new type of oral hypoglycemic drug for treating T2DM.     

2型糖尿病伴非酒精性脂肪肝的危险因素分析

目的 探讨2型糖尿病（T2DM）伴非酒精性脂肪肝（NAFLD）患者的相关危险因素.方法 选取T2DM患者122例,根据肝脏彩超检查分为T2DM伴NAFLD组和T2DM不伴NAFLD组.对其腰围、腰臀比（WHR）、BMI、肝功能、血脂、胰岛素抵抗指数（HOMA-IR）进行比较分析.结果 与单纯T2DM组相比,T2DM伴NAFLD组的腰围、WHR、BMI、TC、TG、LDL-C、ALT、HOMA-IR升高（P＜0.05）.多元逐步回归分析显示,TG、腰围、BMI、HOMAIR是NAFLD的独立危险因素.结论 T2DM伴NAFLD患者存在多种代谢异常,其中肥胖、TG、胰岛素抵抗对其影响最大.     

伊格列净联合其他口服降糖药治疗2型糖尿病的有效性及安全性的系统评价

目的:系统评价伊格列净与其他口服降糖药联合治疗2型糖尿病的有效性和安全性,为其临床应用提供依据。方法:检索PubMed、Cochrane图书馆、Embase、Medline、中国知网、万方、维普、中国生物医学文献数据库中伊格列净联合其他口服降糖药治疗2型糖尿病的随机对照试验(randomized controlled trial,RCT),检索时限为建库起至2016年12月,对纳入研究进行质量评价和Meta分析。结果:5项RCT符合纳入标准,共计863例患者。Meta分析结果显示:与安慰剂组相比,使用伊格列净联用其他口服降糖药治疗患者的糖化血红蛋白水平和空腹血糖水平降低更明显[MD=-0.82,95%CI(-1.17,-0.46),P<0.05;-29.53,95%CI(-40.55,-18.50),P<0.05],而HbA1c<7.0%的比例更高[OR=3.70,95%CI(2.46,5.58),P<0.05]。安全性方面,伊格列净联用其他口服降糖药发生低血糖、尿路感染以及生殖道感染的风险和安慰剂组相比差异无显著性[OR=1.57,95%CI(0.43,5.71),P>0.05;OR=0.98,95%CI(0.42,2.25),P>0.05;OR=0.46,95%CI(0.12,1.74),P>0.05]。结论:与安慰剂组相比,伊格列净联用其他口服降糖药治疗能更加有效地降低糖化血红蛋白以及空腹血糖水平,且发生低血糖等不良反应的风险低。受纳入研究方法学限制,该结论尚需大样本、多中心的RCT进一步验证。     

Drugs for the treatment of pediatric type 2 diabetes mellitus and related co-morbidities

Introduction: The continuing global epidemic of obesity in adolescents has raised the prevalence of type 2 diabetes mellitus (T2DM). Despite the wealth of information concerning T2DM in adults, rare data are available targeting treatment of T2DM in pediatric.

Areas covered: This article has reviewed clinical practice guidelines, particularly the American Diabetes Association and the Pediatric Endocrine Society consensus, jointly with clinical trial data available in databases with respect to the use of available pharmacological options to treat T2DM and its complications in youth.

Expert opinion: The use of other pharmacological treatments of T2DM in addition to metformin and insulin entails several problems. Since rare studies have been conducted on the medications available to manage T2DM in children, treating them may be more difficult than that of adults. It needs longer and larger size clinical trials along with better pharmacological agents to affect various pathophysiological mechanisms of diabetes. Meanwhile, the efficacy and safety of combinations therapies should be completed in preclinical and clinical phases.     

利拉鲁肽和西格列汀在治疗2型糖尿病中的长期益处对比

目的：比较利拉鲁肽和西格列汀在治疗中国2型糖尿病（T2DM）患者中的长期临床和成本益处。方法：数据来源于一项随机对照试验（NCT02008682）,2型糖尿病患者随机分为注射利拉鲁肽1.2 mg·d^-1和口服西格列汀100 mg·d^-1。根据已发表和验证的CORE糖尿病模型,对临床结果和直接费用进行长期预测。未来成本和临床结果的贴现率为每年0%和5%。并进行敏感性分析。结果：与西格列汀相比,使用利拉鲁肽的预期寿命（14.12年 vs. 13.89年）和健康调整生命年[9.11 vs. 8.91（QALYs）]延长,并通过有效控制血糖,减少了肾病、心血管疾病、眼科、糖尿病足等相关并发症的发生。利拉鲁肽1.2 mg比西他列汀的增量成本效益比增加了72 101元/QALY。敏感性分析结果表明,使用利拉鲁肽的QALY和治疗成本均高于西格列汀,并且改善的血糖控制可能是临床获益的主要影响因素。结论：利拉鲁肽加入二甲双胍单药治疗可以改善健康调整生命年,是治疗T2DM的一种经济有效的方法。     

2型糖尿病血浆代谢组学生物标志物鉴定

目的：验证谷氨酸（glutamate,Glu）、天冬酰胺（asparagine,Asn）、棕榈酸（palmitic acid,PA）和油酸（oleic acid,OA）与2型糖尿病（type 2 diabetes mellitus,T2DM）患病风险的关联,鉴定T2DM的早期标志物。方法：选择新发T2DM患者217例、空腹血糖受损（impaired fasting blood glucose,IFG）患者220例及216例健康者,收集人群空腹血液,采用液相色谱-质谱联用仪检测血浆中代谢物浓度。结果：高浓度Glu （OR=1.45,95% CI：1.09~1.93）、PA （OR=1.05,95% CI：1.02~1.07）和OA （OR=1.06,95% CI：1.03~1.09）会增加T2DM患病风险,且Glu水平增加还会提高IFG风险（OR=2.00,95% CI：1.42~2.80）。随着Asn浓度的增加,T2DM患病风险显著降低（OR=0.63,95% CI：0.54~0.74）。此外,PA、Glu和Asn联合BMI鉴别T2DM效果最好。结论： PA、OA、Glu水平升高是T2DM的危险因素,而Asn水平升高则是T2DM的保护因素。以上代谢物可能是T2DM潜在生物标志物,为T2DM的临床筛查、早期治疗与预防、新药研发靶点提供新的思路和策略。     

Ertugliflozin as a monotherapy for the treatment of type 2 diabetes

ABSTRACT

Introduction: Sodium-dependent glucose transporter 2 (SGLT2) inhibitors are novel, potent oral anti-diabetic agents in a β-cell function-independent manner, inhibiting SGLT2-mediated renal glucose reabsorption and thus increasing urinary glucose excretion. Ertugliflozin (Steglatro^TM) is a new oral SGLT2 inhibitor for the treatment of patients with type 2 diabetes mellitus (T2DM) as a monotherapy or in combination with other anti-diabetic agents.

Areas covered: This review summarizes the collected data concerning the pharmacokinetics, clinical efficacy, as well as safety and tolerability profiles of ertugliflozin given as a monotherapy for the management of T2DM.

Expert opinion: Good glycemic control is crucial to the management of T2DM, and accordingly, anti-diabetic agents with various anti-hyperglycemic mechanisms are developed one after another. Based on the available clinical trials of ertugliflozin as a monotherapy for T2DM, it could be found that ertugliflozin effectively improves the glycemic control, body weight and blood pressure of patients with a low risk of hypoglycemia. It is also found that ertugliflozin moderately reduces their blood pressure, which is beneficial for decreasing the risk of cardiovascular disease. These attributes show the good potential of ertugliflozin as an adjunct treatment to diet and exercise for improving glycemic control in patients with T2DM.