口服药物治疗2型糖尿病

<正>研究背景随着生活方式改变,糖尿病发病率逐年上升,严重影响着人们的生活质量。其中,2型糖尿病是最常见的糖尿病类型,其发病风险随着年龄增大而增大。另外,肥胖也是2型糖尿病发病的重要危险因素。2型糖尿病的治疗主要包括生活方式干预和药物治疗,国内已上市的降糖药物有口服降糖药和注射药物,如胰岛素、GLP-1受体激动剂。大部分诊断为2型糖尿病的患者主要接受口服降糖药物治疗。2017年1月,     

胰岛素增敏剂-文迪雅治疗2型糖尿病的临床观察

目的对胰岛素增敏剂-马来酸罗格列酮（文迪雅）联合其他降糖药物治疗2型糖尿病的临床疗效及安全性进行观察。方法对30例2型糖尿病患者进行为期12周的文迪雅治疗观察。结果文迪雅治疗12周前后相比，患者FBG、PG2h、HbA1c水平均有显著下降。治疗后体重略有增加，TG水平有下降，TC、HDL—C、LDL—C无明显变化。收缩压和舒张压均有降低。结论文迪雅用于原降糖治疗效果不满意的2型糖尿病患者，可显著降低糖化血红蛋白、空腹及餐后血糖，提高胰岛素敏感性，减少胰岛素抵抗，未见肝肾功能损害等严重药物不良反应，是治疗2型糖尿病的有效和安全的新型口服降糖药。     

糖尿病治疗需“斤斤计较”

全球范围内,2型糖尿病发病率的增加与越来越高的肥胖患病率密切相关。体重增加是2型糖尿病的主要危险因子,严重影响患者的生活质量;更值得关注的是,最有效的降糖手段——胰岛素注射,却往往使2型糖尿病患者的体重进一步增加,给本已超重的患者身心健康带来沉重负担。     

2型糖尿病合理用药策略

2型糖尿病是我国主要慢性疾病之一,而其控制状况不容乐观。降糖药物的使用是控制血糖的重要利器之一,糖尿病的药物治疗按作用机制和结构主要分为胰岛素促泌剂、双胍类、噻唑烷二酮类药物、糖苷酶抑制剂、DPP-Ⅳ抑制剂、GLP-1、胰岛素及其类似物等。本文概述临床常用降糖药物的药理机制、作用特点及其特性,并提出适时启用胰岛素、简单化原则、合理联用、个体化原则及兼顾安全性、性价比的合理使用降糖药物策略。     

降糖药的“副业”减肥作用

<正>我父亲身体肥胖又患有2型糖尿病,医师建议他服用二甲双胍,既能降糖,又能减肥,但疗效并不理想,听说还有其他的降糖药也有类似作用,请问是什么药?湖北读者岳峰二甲双胍是目前比较普遍使用的降糖药物,但它尚可减肥,因此适合用于肥胖型的2型糖尿病患者,除此之外,目前还发现由胃肠道细胞分泌的胰高糖素样肽-1(GLP-1)和葡萄糖依赖性胰岛素多肽(GLP),可以调节胰岛素细胞功能,增强     

治疗2型糖尿病新药——磷酸西他列汀

2型糖尿病是由胰岛素抵抗或胰岛B细胞功能受损引起，其可诱发糖尿病肾病、心肌梗死、脑卒中等多种并发症。现治疗2型糖尿病的药物多种，虽然降糖作用较为理想，但均有一些副作用而影响患者坚持用药，即达不到较好的血糖控制目的。磺酰脲类和胰岛素易导致低血糖，使患者体重增加；噻唑烷二酮类也易引起患者体重增加；二甲双胍的胃肠道耐受性不好。现介绍一种新型的治疗糖尿病的药物，系二肽基肽酶Ⅳ（DPP-4）抑制剂，能够血糖依赖性地增加胰岛素的分泌，降糖作用较为适中，而且不会导致低血糖的发生，无增加体重、恶心、呕吐等副作用，还可能具有保护胰岛B细胞的作用，适用于不能耐受其它降糖药物的2型糖尿病患者。     

二甲双胍缓释剂型对糖尿病患者治疗依从性的影响

英国前瞻性糖尿病研究（UKPDS）及许多大型临床研究证明,二甲双胍降糖作用强而有效,是目前超重或肥胖2型糖尿病患者一线治疗药物。二甲双胍除安全有效的降糖作用外,还可改善胰岛素抵抗、控制体重、调节血脂、血压,减轻高凝状态、改善血管反应性,     

二甲双胍对老年2型糖尿病患者的疗效及安全性

二甲双胍是应用广泛的降糖药物(胰岛素增敏剂)，具有磺脲类药物同样的降糖效果，主要是抑制糖异生和肝糖分解，加强外周肌肉组织和肝组织受体与胰岛素的结合或受体后环节而增加胰岛素介导的葡萄糖的利用；特别是不刺激胰岛细胞分泌，不致于导致胰岛功能的衰竭，并且尚可降低胰岛素抵抗及减轻体重，其主要副作用是乳酸酸血症。已往的研究选择的病例多为中年或中老年患者，作者观察了二甲双胍对老年2型糖尿病患者的疗效及安全性，现报告如下：     

地特胰岛素对肥胖或超重2型糖尿病患者体重的影响分析

目的:分析地特胰岛素对肥胖或超重2型糖尿病患者体重的影响。方法:选取2013年1月~2015年1月某院收治的86例肥胖或超重2型糖尿病患者为研究对象,均常规口服降糖药物,同时加用地特胰岛素治疗,对比观察患者治疗前后FBG(空腹血糖)、HbA1c(糖化血红蛋白)、BMI(体质量指数)、体重、腰围及臀围变化情况。结果:治疗前后患者臀围比较,无统计学意义(P0.05);治疗后患者BMI、FBG、HbA1c、体重及腰围等方面与治疗前比较,有统计学意义(P0.05)。结论:肥胖或超重2型糖尿病患者采用地特胰岛素治疗,在有效控制其血糖水平的同时,还一定程度控制了患者体重,值得推广。     

FDA批准Belviq治疗成人超重或肥胖症

<正>2012年6月27日,FDA批准Arena公司的Belviq(lorcaserin hydrochloride)上市,作为长期控制体重的减肥药物,与低热量饮食和运动结合,治疗体重指数≥27的且患有肥胖相关并发症如2型糖尿病的成人超重或肥胖患者。Belviq为近十年首个获     

Off-label use of exenatide for the management of insulin-resistant type 1 diabetes mellitus in an obese patient with human immunodeficiency virus infection

Exenatide is an incretin mimetic indicated for the treatment of type 2 diabetes mellitus in combination with a sulfonylurea, a thiazolidinedione, metformin, or metformin plus a sulfonylurea or thiazolidinedione. Exenatide lowers postprandial blood glucose levels by stimulating glucose-dependent insulin secretion, inhibiting glucagon secretion, slowing gastric emptying, and increasing satiety. Therapy with exenatide often results in weight loss, which further assists in decreasing insulin resistance. This feature makes the drug an attractive therapeutic option for obese patients. We report the successful off-label use of exenatide in an obese, 40-year-old man with type 1 diabetes and human immunodeficiency virus (HIV) infection who had gastrointestinal intolerance to pramlintide. The patient had experienced a dramatic weight gain secondary to his antiretroviral drugs. This weight gain led to insulin resistance and the development of type 2 diabetes; thus he had characteristics of both types 1 and 2 diabetes, or double diabetes. Before the start of exenatide therapy, he weighed 123 kg, had a body mass index of 42.3 kg/m(2), and had a suboptimal hemoglobin A(1c) value of 8.7%. After 11 months of therapy, the patient lost 24 kg (19.5% of his body weight) and achieved a hemoglobin A(1c) value of 7.3%. His basal insulin requirement was reduced by 25%, and his use of short-acting insulin before breakfast and before dinner was discontinued. In addition, the patient's quality of life substantially improved, as he was able to return to work and exercise after being nearly incapacitated by his weight. To our knowledge, this is the first published case report of the use of exenatide in a patient with type 1 diabetes mellitus or human immunodeficiency virus infection. Given this experience, exenatide may prove to be a useful alternative in selected patients with type 1 diabetes.     

Treatment of diabetes in experimental animals by metallocomplexes

The number of patients suffered from diabetes mellitus has increased over the decades probably because of both lifestyle- and diet-changes. There are two types of diabetes mellitus. Type 1 diabetes mellitus is due to the autoimmune-mediated destruction of pancreatic B cells, which results in absolute insulin deficiency, thus the patients require insulin injections. Type 2 diabetes mellitus is due to the insulin resistance and abnormal insulin secretion, thus the patients require exercise, diet control and/or oral hypoglycemic medicines. Each treatment, however, has some problems involving physical and mental burden, and formation of self-antibodies for insulin injections, and the severe side effects and discontinuation of insulin synthesis in the pancreas for hypoglycemic medicines. To overcome these important problems and find the replacements for the insulin injections and synthetic medicines, we attempted to develop new antidiabetic metallocomplexes with novel structures and mechanisms. In 1990, we first presented orally active vanadyl (+4 oxidation state of oxo-vanadium) complexes including vanadyl-cysteine methyl ester complex, which normalized hyperglycemia in the streptozocin (STZ)-induced type 1 diabetic rats. Based on these findings, we have developed a wide variety of vanadyl complexes with different coordination environments around vanadyl ion. Following the study, we also challenged to develop orally active zinc complexes since 2002. This review focuses on our recent development of vanadyl and zinc complexes for anti-diabetic and anti-metabolic syndromes, together with the propose for the possible action mechanism of these complexes in adipocytes.     

二肽基肽酶Ⅳ抑制剂辅助胰岛素治疗1型糖尿病的研究进展

二肽基肽酶Ⅳ（DPP-4）抑制剂为一类在2型糖尿病中应用广泛的口服降糖药,其疗效确切、给药方便、总体耐受性好,但目前尚未被批准用于1型糖尿病。国内外相关文献表明在1型糖尿病患者体内DPP-4抑制剂可以辅助胰岛素改善血糖、保护胰岛β细胞功能、降低谷氨酸脱羧酶抗体（GADA）滴度、减少胰岛素剂量,且不增加低血糖风险和体质量。因此,DPP-4抑制剂可能可作为1型糖尿病患者胰岛素的辅助治疗,作用机制可能源于其抑制胰岛α细胞分泌胰高血糖素,通过免疫机制使胰岛β细胞免受摧毁。     

新型钠-葡萄糖共转运蛋白2抑制剂现状及其研发动态

钠-葡萄糖共转运蛋白2（SGLT-2）为2型糖尿病治疗的新靶点。SGLT-2抑制剂具有全新的降糖机制,其对能量平衡的负调控、降低体重、不依赖胰岛素降低血糖等特点,成为各大药企研发的热点。本文综述该类药物的降糖机制,分析现阶段SGLT-2抑制剂的最新研发动态。     

初发2型糖尿病胰岛素或口服降糖药治疗对改善B细胞功能的研究

目的对初发2型糖尿病患者进行早期的强化治疗,并探讨改善B细胞功能的可能机制。方法选择50例患者使用胰岛素泵治疗,并与口服降糖药物治疗的50例患者做比较,观察两组患者治疗后空腹血糖、胰岛B细胞功能指数、胰岛素抵抗指数（Homa-IR）以及空腹C肽水平的变化。结果治疗后两组患者空腹血糖均值均恢复到正常范围,且差异无统计学意义（P〉0.05）,观察组Homa-β和糖化血红蛋白比值显著优于对照组（P〈0.05）,两组Homa-IR间差异无统计学意义（P〉0.05）,观察组空腹C肽水平高于对照组（P〈0.05）。结论高糖毒性的解除和胰岛细胞休息学说在2型糖尿病的发生发展中均占据重要地位。     

Current management strategies for coexisting diabetes mellitus and obesity

Besides genetic predisposition, obesity is the most important risk factor for the development of diabetes mellitus. Weight reduction has been shown to markedly improve blood glucose control and vascular risk factors associated with insulin resistance in obese individuals with type 2 diabetes. Therapeutic strategies for the obese diabetic patient include: (i) promoting weight loss, through lifestyle modifications (low-calorie diet and exercise) and antiobesity drugs (orlistat, sibutramine, etc.); (ii) improving blood glucose control, through agents decreasing insulin resistance (metformin or thiazolidinediones, e.g. pioglitazone and rosiglitazone) or insulin needs (alpha-glucosidase inhibitors, e.g. acarbose) in preference to agents stimulating defective insulin secretion (sulphonylureas, meglitinide analogues); and (iii) treating common associated risk factors, such as arterial hypertension and dyslipidaemias, to improve cardiovascular prognosis. Whenever insulin is required by the obese diabetic patient after failure to respond to oral drugs, it should be preferably prescribed in combination with an oral agent, more particularly metformin or acarbose, or possibly a thiazolidinedione. When morbid obesity is present, both restoring a good glycaemic control and correcting associated risk factors can only be obtained through a marked and sustained weight loss. This objective justifies more aggressive weight reduction programmes, including very-low-calorie diets and bariatric surgery, but only within a multidisciplinary approach and long-term strategy.     

Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug–drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug–drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.     

甘精胰岛素强化治疗新诊断2型糖尿病疗效观察

目的:观察睡前皮下注射甘精胰岛素与中效胰岛素(NPH)对新诊断2型糖尿病患者的疗效。方法:将64例新诊断2型糖尿病患者分为A、B组,分别睡前皮下注射甘精胰岛素和睡前皮下注射NPH,2组均在饮食控制及一定活动量基础上皮下注射短效胰岛素。比较2组治疗后平均空腹血糖、血糖达标时间、日内血糖漂移、低血糖发生率及胰岛素总用量。结果:甘精胰岛素组在治疗后平均空腹血糖、血糖达标时间、日内血糖漂移、低血糖发生率等方面均低于NPH组(P<0.05)。结论:甘精胰岛素联合短效胰岛素治疗新诊断2型糖尿病疗效好,安全性高。     

2006～2008年1～3季度杭州地区门诊患者降糖药应用分析

目地：了解杭州地区糖尿病患者的用药需求,为临床合理用药提供参考依据。方法：采用《医院处方分析》课题组（杭州地区）提供的数据,对杭州地区2006年1～3季度、2007年1～3季度及2008年1～3季度门诊降糖药的使用情况进行动态分析,应用TPD排序、总治疗人次日分析以及药理学分类,对降糖药进行排序以及统计分析。结果：口服制剂中二甲双胍和阿卡波糖（拜唐苹）连续3年分居第1和第2位,2006年及2007年瑞格列奈（孚来迪）居第3位,2008年第3位被盐酸二甲双胍（格华止）取代。注射剂型方面,诺和灵30R及优泌林70/30居于近3年的前两位,甘舒霖30R和诺和灵50R分居第3位。结论：随糖尿病发病率的增高,降糖药的种类逐年增多。杭州地区的降糖药目前以口服降糖药为主,从药理学看主要为促进胰岛素分泌类药物,但α-葡萄糖苷酶抑制剂的用量逐年上升。胰岛素方面以卡式瓶应用为主,主要使用混合型胰岛素。     

Exenatide: A New Promising Antidiabetic Agent

Exenatide is a unique agent which can effectively control blood glucose levels in type 2 diabetes mellitus without producing dangerous adverse effects. In addition, it can lower body weight which is very essential for the treatment of obese type 2 diabetes mellitus patients. Since it can delay the destruction of islet beta-cells, type 2 diabetes mellitus patients are not rapidly converted to type 1 diabetes mellitus and ultimately appearance of complications of the disease is halted or delayed. Its long-acting-release formula, which would be used once per week, simultaneously retaining all the properties of twice-daily subcutaneous administration, is undergoing clinical trial. This drug is considered as an adjunct to metformin/sulfonylureas/insulin.