Glycemic control and the first use of oral antidiabetic agents among patients with type 2 diabetes mellitus

Abstract

Objective:

Examine how patients diagnosed with type 2 diabetes mellitus (T2DM) are treated with oral antidiabetic (OAD) agents and the relationship between treatment patterns and glycemic control.     

Oral antidiabetic agents: current role in type 2 diabetes mellitus

Type 2 diabetes mellitus is a progressive and complex disorder that is difficult to treat effectively in the long term. The majority of patients are overweight or obese at diagnosis and will be unable to achieve or sustain near normoglycaemia without oral antidiabetic agents; a sizeable proportion of patients will eventually require insulin therapy to maintain long-term glycaemic control, either as monotherapy or in conjunction with oral antidiabetic therapy. The frequent need for escalating therapy is held to reflect progressive loss of islet beta-cell function, usually in the presence of obesity-related insulin resistance. Today's clinicians are presented with an extensive range of oral antidiabetic drugs for type 2 diabetes. The main classes are heterogeneous in their modes of action, safety profiles and tolerability. These main classes include agents that stimulate insulin secretion (sulphonylureas and rapid-acting secretagogues), reduce hepatic glucose production (biguanides), delay digestion and absorption of intestinal carbohydrate (alpha-glucosidase inhibitors) or improve insulin action (thiazolidinediones). The UKPDS (United Kingdom Prospective Diabetes Study) demonstrated the benefits of intensified glycaemic control on microvascular complications in newly diagnosed patients with type 2 diabetes. However, the picture was less clearcut with regard to macrovascular disease, with neither sulphonylureas nor insulin significantly reducing cardiovascular events. The impact of oral antidiabetic agents on atherosclerosis--beyond expected effects on glycaemic control--is an increasingly important consideration. In the UKPDS, overweight and obese patients randomised to initial monotherapy with metformin experienced significant reductions in myocardial infarction and diabetes-related deaths. Metformin does not promote weight gain and has beneficial effects on several cardiovascular risk factors. Accordingly, metformin is widely regarded as the drug of choice for most patients with type 2 diabetes. Concern about cardiovascular safety of sulphonylureas has largely dissipated with generally reassuring results from clinical trials, including the UKPDS. Encouragingly, the recent Steno-2 Study showed that intensive target-driven, multifactorial approach to management, based around a sulphonylurea, reduced the risk of both micro- and macrovascular complications in high-risk patients. Theoretical advantages of selectively targeting postprandial hyperglycaemia require confirmation in clinical trials of drugs with preferential effects on this facet of hyperglycaemia are currently in progress. The insulin-sensitising thiazolidinedione class of antidiabetic agents has potentially advantageous effects on multiple components of the metabolic syndrome; the results of clinical trials with cardiovascular endpoints are awaited. The selection of initial monotherapy is based on a clinical and biochemical assessment of the patient, safety considerations being paramount. In some circumstances, for example pregnancy or severe hepatic or renal impairment, insulin may be the treatment of choice when nonpharmacological measures prove inadequate. Insulin is also required for metabolic decompensation, that is, incipient or actual diabetic ketoacidosis, or non-ketotic hyperosmolar hyperglycaemia. Certain comorbidities, for example presentation with myocardial infarction during other acute intercurrent illness, may make insulin the best option. Oral antidiabetic agents should be initiated at a low dose and titrated up according to glycaemic response, as judged by measurement of glycosylated haemoglobin (HbA1c) concentration, supplemented in some patients by self monitoring of capillary blood glucose. The average glucose-lowering effect of the major classes of oral antidiabetic agents is broadly similar (averaging a 1-2% reduction in HbA1c), alpha-glucosidase inhibitors being rather less effective. Tailoring the treatment to the individual patient is an important principle. Doses are gradually titrated up according to response. However, the maximal glucose-lowering action for sulphonylureas is usually attained at appreciably lower doses (approximately 50%) than the manufacturers' recommended daily maximum. Combinations of certain agents, for example a secretagogue plus a biguanide or a thiazolidinedione, are logical and widely used, and combination preparations are now available in some countries. While the benefits of metformin added to a sulphonylurea were initially less favourable in the UKPDS, longer-term data have allayed concern. When considering long-term therapy, issues such as tolerability and convenience are important additional considerations. Neither sulphonylureas nor biguanides are able to appreciably alter the rate of progression of hyperglycaemia in patients with type 2 diabetes. Preliminary data suggesting that thiazolidinediones may provide better long-term glycaemic stability are currently being tested in clinical trials; current evidence, while encouraging, is not conclusive. Delayed progression from glucose intolerance to type 2 diabetes in high-risk individuals with glucose intolerance has been demonstrated with troglitazone, metformin and acarbose. However, intensive lifestyle intervention can be more effective than drug therapy, at least in the setting of interventional clinical trials. No antidiabetic drugs are presently licensed for use in prediabetic individuals.     

Oral antidiabetic agents in type 2 diabetes

ABSTRACT

Background: Oral antidiabetic agents differ with regard to mechanisms of action, hemoglobin A_1c-lowering efficacy, safety, and tolerability. Traditional agents consist of those that enhance insulin secretion (i.e., sulfonylureas and glinides), those that enhance insulin sensitivity (i.e., metformin and the thiazolidinediones), and those that inhibit intestinal carbohydrate absorption (i.e., the α?glucosidase inhibitors). New oral agents include the dipeptidyl peptidase-4 (DPP?4) inhibitors, which potentiate the activity of the incretin glucagon-like peptide 1 and enhance glucose-dependent insulin secretion.

Scope: We review the characteristics of the traditional oral agents and these newer additions to the pharma­ceutical armamentarium. Abstracts and original clinical and preclinical reports in the English language were identified for review based on MEDLINE literature searches (1970–2006) and abstract collections from major diabetes meetings.

Conclusions: Traditional oral agents provide significant treatment benefits for diabetic patients, including reduction in risk of microvascular complications. However, most patients with type 2 diabetes do not achieve target glycemic levels with traditional therapies, and these agents are also associated with hypoglycemia, weight gain, and poor tolerability. Oral DPP?4 inhibitors offer the potential for significant improvement in glycemic control without hypoglycemia or weight gain, although long-term durability of glycemic control (>?52 weeks) has not been established.     

2型糖尿病患者口服降糖药物控制血糖达标与血脂水平相关性探讨

目的 探讨2型糖尿病患者单纯使用口服降糖药物控制血糖达标与血脂水平的相关性.方法 检测173例2型糖尿病患者单纯使用口服降糖药物治疗血糖达标状况与血脂水平,以HbA1c＜ 7％作为血糖控制达标标准,将患者分为达标组和未达标组,比较两组血脂控制水平.结果 173例患者中,平均HbA1c 7.9％,血糖达标率43.4％;血糖达标组甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇等控制水平均优于血糖未达标组(t=-2.437、-2.067、2.005、- 2.984,P=0.016、0.040、0.047、0.003).结论 2型糖尿病患者单纯使用口服降糖药物控制血糖达标的同时应关注对血脂水平的影响.     

硒酵母对2型糖尿病患者血清C肽水平的影响

目的观察硒酵母对2型糖尿病(T2DM)患者血清C肽水平的影响。方法选取120例T2DM患者,依据随机原则分为:对照组(60例,予以常规降糖等正规治疗措施)和治疗组(60例,在常规治疗基础上加用硒酵母片治疗,至少应用3个月)。治疗1年后比较治疗前后两组患者的空腹C肽水平、餐后2 h C肽、餐后2 h C肽较空腹C肽倍数、糖化血红蛋白(Hb A1c)、空腹血糖(FPG)及餐后2 h血糖(PPG)差异。应用Pearson相关性分析分别评估硒酵母疗程与空腹C肽水平、餐后2 h C肽的相关性。结果治疗前两组上述各项指标差异均无统计学意义(P>0.05)。治疗后与对照组相比,治疗组的空腹C肽水平、餐后2 h C肽、Hb A1c、FPG与PPG显著改善(P<0.05),而两组餐后2 h C肽较空腹C肽倍数比较差异无统计学意义(P>0.05)。硒酵母疗程与空腹C肽水平(r=0.613,P=0.021)、餐后2 h C肽(r=0.574,P=0.038)均存在正相关。结论硒酵母可提高T2DM患者空腹及餐后2 h C肽水平,改善血糖控制程度。     

Optimizing antidiabetic treatment options for patients with type 2 diabetes mellitus and cardiovascular comorbidities

Cardiovascular disease is the leading cause of death in patients with diabetes mellitus and represents a persistent risk that is inextricably linked to the diabetic disease state. The growing number of United States Food and Drug Administration-approved antidiabetic agents provides a wide range of therapeutic options, both as monotherapy and combination therapy, for treating hyperglycemia in patients with type 2 diabetes. Long-term clinical experience with many of these agents has revealed nonglycemic effects on lipid levels, inflammation, and cardiovascular function. Although some of these agents can improve cardiovascular disease risk in patients with diabetes, others may increase the risk and may be prohibited from use in certain populations. Thus, the effect of antidiabetic agents on cardiovascular health and safety must be considered when selecting the most appropriate therapy. A review of the current literature was undertaken to examine the effects of antidiabetic agents on cardiovascular disease, and with the help of illustrative patient case examples, useful information is provided for clinicians to individualize therapy for patients with type 2 diabetes.     

门诊2型糖尿病患者口服降糖药物应用及代谢指标控制的调查分析

目的:评估门诊2型糖尿病(T2DM)患者口服降糖药物应用及主要代谢指标控制达标情况。方法:随机调查347例口服药物治疗的门诊T2DM患者,收集患者的人口学资料、口服降糖药物应用及血糖、血压、血脂等指标,并分析慢性并发症发生情况。根据《中国2型糖尿病防治指南》(2010年版)分析代谢指标达标情况。结果:347例患者中口服降糖药物使用比例最高的为二甲双胍(52.2%),其次为磺脲类(51.6%)。治疗方案中单药治疗占35.2%,2种及3种以上药物分别占49.0%及15.8%。糖化血红蛋白(HbA1c)、空腹血糖、餐后血糖的达标率分别为59.1%,73.2%,71.8%。33.4%的患者血压达标,各血脂指标仅有40%患者达标。患者用药种类随糖尿病病程延长而增加,而单药、两药及三药治疗的患者HbA1c水平无差异。结论:根据《中国2型糖尿病防治指南》(2010年版),门诊T2DM患者血糖达标率明显提高,但血压、血脂达标率较低,仍有40.9%的患者血糖未能满意控制。     

2型糖尿病口服降糖药的应用策略及安全性评价

糖尿病(Diabetes mellitus,DM)是一组由于遗传和环境因素相互作用所致的综合征,以慢性血糖水平增高为特征的代谢疾病群.……     

The treatment of type 1 diabetes mellitus with agents approved for type 2 diabetes mellitus

Introduction: The management of type 1 diabetes remains a challenge for clinicians. Current practice is to administer insulin analogues to best mimic normal physiological insulin profiles. However, despite our best efforts the majority of individuals with type 1 diabetes continue to suffer from suboptimal glucose control, significant hypoglycemia and microvascular tissue complications of the disease. There is thus a significant unmet need in the treatment of T1DM to obtain better glycemic control.

Areas covered: We discuss the use of α-glucosidase inhibitors, dipeptidyl-peptidase inhibitors, glucagon-like peptide 1 agonists, biguanides, thiazolidinediones and sodium glucose co-transporter 2 inhibitors in individuals with T1DM.

Expert opinion: Non-insulin therapies present a unique and exciting adjunctive treatment for individuals with type 1 diabetes. Although data are scarce, the classes of medications discussed help to lower glucose, decrease glycemic excursions and in some cases improve body weight, along with allowing dose reductions in total daily insulin. Glucagon-like peptide 1 agonists and sodium glucose co-transporter 2 inhibitors, in particular, have been demonstrated to provide clinical improvements in individuals with T1DM and we feel their use can be explored in obese, insulin-resistant patients with T1DM, those with frequent and significant glycemic excursions or individuals with persistently elevated hemoglobin A1c.     

Efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus: comparison with other oral antihyperglycaemic agents

Diabetes mellitus is a debilitating disease that is estimated to affect 366 million people by the year 2030. Type 2 diabetes mellitus (T2DM) is characterized by a progressive decline in pancreatic β-cell function and increased insulin resistance, and accounts for approximately 90% of people with diabetes. Oral antihyperglycaemic agents are extensively used in the treatment of T2DM. Thiazolidinediones are insulin sensitizers developed specifically for T2DM, which act via activation of peroxisome proliferator-activated receptors (PPARs). Pioglitazone is a thiazolidinedione that displays high affinity for PPARγ(1) and PPARγ(2), which are predominately expressed in adipose tissue. This review examines the published literature comparing the efficacy and tolerability of pioglitazone with other oral antihyperglycaemic agents in the treatment of patients with T2DM. Glycosylated haemoglobin, fasting glucose, insulin parameters and β-cell function are all improved with pioglitazone treatment, with efficacy similar to third-generation sulfonylureas, metformin and dipeptidyl peptidase-4 inhibitors. Pioglitazone reduces vascular risk and inflammatory markers, and improves carotid intima media thickness independent of its glycaemic effect. When compared with rosiglitazone, pioglitazone is associated with a reduction in the risk of hospitalization for acute myocardial infarction. Blood pressure is reduced and lipid profiles are favourably improved with pioglitazone; however, an increased risk for the development/exacerbation of heart failure, which is related to the increased incidence of oedema due to fluid retention, and fractures remain a concern. A low incidence of hypoglycaemia is observed with pioglitazone, especially compared with sulfonylureas. In conclusion, pioglitazone is an effective oral antihyperglycaemic agent with additional cardiovascular and lipid benefits that allows for the successful management of patients with T2DM.     

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。     

The current aspects of the pharmacological correction of hyperglycemia in patients with non-insulin-dependent diabetes mellitus (type 2)

Data on the mechanisms of developing of hyperglycemia in patients with diabetes mellitus (type 2) are analyzed and reviewed. The current concept of hypoglycemic therapy aimed both at amelioration of hyperglycemia symptoms and reduction of the risk of diabetic micro- and macroangiopathies is considered. The main directions of pharmacological action of hypoglycemic drugs (both in use and in the stage of design) and data of the efficiency and possible incidental action are presented.     

Ⅱ型糖尿病患者血脂水平分析

目的通过对Ⅱ型糖尿病患者血脂水平分析,有效地控制糖尿病并发症的发生。方法用7170A生化分析仪检测72例Ⅱ型糖尿病患者和83例健康体检者血清中的TG、TC、HDL-C、LDL-C。结果Ⅱ型糖尿病患者血清中的TG、TC、LDL-C均比健康对照组高,HDL-C比健康对照组低。结论Ⅱ型糖尿病患者均有脂类代谢异常。     

Cost-effectiveness of oral hypoglycaemic agents for the treatment of type 2 diabetes mellitus

Diabetes is a public health problem worldwide. Its treatment includes controlling hyperglycaemia, initially through changes in lifestyle such as diet, exercise and weight loss. UK Prospective Diabetes Study results showed that intensive treatment to achieve glycaemic control in patients with type 2 diabetes reduces the risk of diabetes-related complications. Typically, patients initially receive monotherapy with oral hypoglycaemic agents but usually progress to combination therapy or insulin. In the short term, the cost of achieving glycaemic control can be substantial, particularly when combination therapy is required. However, additional treatment costs of achieving recommended glycaemic control levels are predicted to be at least partially offset in the long term by the reduction of diabetes-related complications and their related management costs.     

罗格列酮对2型糖尿病患者血清抵抗素的影响

目的研究罗格列酮（ROS）对2型糖尿病患者血清抵抗素（resistin）水平的影响。方法选择初诊2型糖尿病患者56例,随机分为治疗组36例,对照组20例,两组均给予一般治疗,治疗组另外给予口服罗格列酮（ROS）4mg,每日1次,总疗程12周,测定指标包括一般项目、血糖和血清胰岛素及抵抗素,以胰岛素抵抗（HOMA）模型评价组织胰岛素敏感性。结果ROS治疗12周后,患者空腹血糖、血清胰岛素水平、胰岛素抵抗指数（HOMA-IR）及血清抵抗素水平均明显降低（P〈0．05）,与对照组比较有明显改善（P〈0．05）。结论ROS能显著降低2型糖尿病患者胰岛素抵抗程度,改善糖代谢,可能与改善人血清抵抗素水平有关。     

初诊2型糖尿病合并代谢综合征患者治疗前后血清ghrelin水平的变化

目的 研究初诊2型糖尿病合并代谢综合征患者血浆血糖、血清胰岛素水平、血脂、胰岛β细胞功能及血清ghrelin水平的变化.方法 同步测定初诊2型糖尿病患者34例,其中合并代谢综合征(MS)患者15例治疗前、治疗后6个月静脉糖耐量试验(IVGTT)时血清、胰岛素、ghrelin、血浆血糖及三酰甘油(TG)、总胆固醇(TC)...