Glyburide/metformin tablets: a new therapeutic option for the management of Type 2 diabetes

Oral antidiabetic combination therapy is a proven means of establishing glycaemic control in the hyperglycaemic, Type 2 diabetic patient, but co-administering two oral antidiabetic agents separately may hinder compliance with therapy. A new single-tablet of glyburide/metformin combination therapy (Glucovance), Bristol-Myers Squibb, Inc.) has recently been developed, which addresses the primary defects of Type 2 diabetes: beta-cell dysfunction and insulin resistance. The glyburide/metformin tablet, taken with meals, is designed to optimise the absorption of glyburide and to address the postprandial glucose rise. Glyburide/metformin tablets are more effective in controlling fasting and postprandial glycaemia than its component monotherapies, at lower doses of metformin and glyburide compared with monotherapy because of the synergy between its glyburide and metformin components. Moreover, a double-blind study showed that glyburide/metformin tablets are more effective than a free combination of glyburide co-administered with metformin in controlling postprandial glucose. Retrospective analyses suggested that glyburide/metformin tablets control glycated haemoglobin (A1C) more effectively than a free combination of glyburide co-administered with metformin, at lower mean doses of glyburide and metformin. The incidence of side effects is lower than separate component therapy for any given A1C. Glyburide/metformin tablets are an effective option for optimising the control of blood glucose in Type 2 diabetic patients and appear to enhance adherence to therapy.     

Rosiglitazone plus metformin: combination therapy for Type 2 diabetes

Type 2 diabetes is a common disease associated with an increased risk of long-term complications, in particular cardiovascular disease. Intervention trials have provided evidence that strict metabolic control can substantially reduce the burden of the disease. However, in order to accomplish this, the pathogenetic defects must be tackled by appropriate therapy. Insulin resistance is a common defect in these patients and it is even more severe in those who are obese. Insulin resistance not only contributes to impaired glucose homeostasis, but also to the development of dyslipidaemia, hypertension, inflammatory response and endothelial dysfunction, thus exacerbating the cardiovascular risk. Improvement of insulin sensitivity can be obtained with metformin and thiazolidinediones. These drugs act through different mechanisms with metformin exerting a prevalent effect on the liver and glitazones improving insulin sensitivity in peripheral tissue. Because of different mechanisms, the association of the two compounds is likely to result in an additive effect. Clinical trials available indicate that the combination of the two drugs results in greater improvement in plasma glucose concentration and HbA_1c as compared to single therapy, without increasing the occurrence of specific side effects. More recently, the two compounds have been associated in the same tablet, thus providing the opportunity for a more convienient treatment that may encourage patient compliance and, at the same time, provide a tool to assess whether a more aggressive intervention on insulin resistance may produce favourable effects on the cardiovascular risk.     

罗格列酮联合二甲双胍治疗初发2型糖尿病疗效与安全性评价

目的探讨罗格列酮与二甲双胍联合治疗初发2型糖尿病的疗效,并评价联合用药的安全性。方法 180例初发2型糖尿病患者随机分为罗格列酮组、二甲双胍组和罗格列酮联合二甲双胍组,每组60例,分别给予罗格列酮、二甲双胍和罗格列酮＋二甲双胍,共治疗24周。观察3组糖化血红蛋白（HbA1c）、空腹血糖（FBG）、餐后2h血糖（2hBG）、胰岛素（BG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）、胰岛素敏感指数（HOMA-IAI）、体重指数（BMI）、总胆固醇（TC）、三酰甘油（TG）,并观察3组的不良反应情况。结果 3组治疗后FBG、2hBG、FINS、HbA1c、TC及TG均较治疗前显著下降（P〈0.05或〈0.01）;罗格列酮联合二甲双胍组FBG、2hBG、BMI较单用罗格列酮及二甲双胍显著下降（P〈0.05）,FINS较二甲双胍组显著下降（P〈0.05）;罗格列酮联合二甲双胍组HOMA-IAI升高程度较其他2组更明显（P〈0.05）。结论罗格列酮联合二甲双胍治疗初发2型糖尿病较二者单用疗效好,可作为理想的用药选择。     

罗格列酮-二甲双胍治疗2型糖尿病疗效评价

胰岛素抵抗及胰岛β细胞功能进行性衰竭是2型糖尿病重要的发病机制.目前应用最广泛的改善胰岛素敏感性的两种药物即马来酸罗格列酮和盐酸二甲双胍,其复合片剂现已成功上市.本品具有良好的血糖控制、减轻胰岛素抵抗和保护胰岛13细胞功能等作用,可改善脂肪代谢和降低心血管事件危险因子及相关标志物水平等.本文简要综述罗格列酮.二甲双胍复方制剂的疗效及安全性.     

Metformin extended release for the treatment of Type 2 diabetes mellitus

Metformin extended release (ER) (Glumetza?, Depomed, Inc.) is a recently approved formulation that provides effective and well-tolerated glycaemic control with once-daily dosing. Metformin ER has similar bioavailability to conventional immediate-release (IR) formulations. In controlled clinical trials, metformin ER provided effective glycaemic control for 24 weeks when administered either as monotherapy or in combination with sulfonylurea. Good glycaemic control was maintained for an additional 24 weeks during an open-label extension study. Once-daily dosing with metformin ER 1500 mg/day was as effective as twice-daily dosing with metformin IR at the same total daily dose. Metformin ER was well tolerated at doses of 1500 or 2000 mg/day, with no increase in the frequency or severity of adverse events at the higher dose.     

The contentious nature of gestational diabetes: diet,insulin, glyburide and metformin

Gestational diabetes (GD) develops because pregnancy increases requirements for insulin secretion while increasing insulin resistance. Women with GD often have impaired pancreatic β-cell compensation for insulin resistance. The nature of GD is currently contentious, with debate about its existence, diagnosis and ramifications for both mother and offspring from pregnancy into later life. Also contentious are the outcomes of intervention with diet, insulin, glyburide (Glynase?, Pharmacia Upjohn) and metformin (Glucophage?, Bristol-Myers Squibb). There is consensus that women with unequivocal GD have a significant risk of adverse perinatal outcomes and increased risk of later type 2 diabetes mellitus. Foetuses from pregnancies with GD have a higher risk of macrosomia (associated with higher rate of birth injuries), asphyxia, and neonatal hypoglycaemia and hyperinsulinaemia. Uncontrolled GD predisposes foetuses to accelerated, excessive fat accumulation, insulin resistance, pancreatic exhaustion secondary to prenatal hyperglycaemia and possible higher risk of child and adult obesity and type 2 diabetes mellitus later in adult life. However, there is no consensus as to whether glucose intolerance of a severity below unequivocal GD is related to adverse maternal, fetal or perinatal outcomes, and whether this relationship is a continuous one. If dietary intervention is not sufficient in the treatment of GD, then, historically, insulin has been added. Recent studies suggest that glyburide may be efficaciously substituted for insulin. Preliminary studies suggest that metformin may have the unique potential to prevent the development of GD.     

β-Cell regeneration: a potential cure for Type 1 diabetes

Type 1 diabetes is a direct result of an autoimmune attack directed at the pancreatic islet cells. Within the islets, which account for 5% of the total pancreatic mass, are insulin-producing β-cells crucial for normal metabolism. Upon destruction of these cells, insulin can no longer be synthesised and secreted and therefore glucose levels must be regulated via exogenous insulin. Research involving regenerating β-cells has made astounding progress in the past two decades, owing greatly to molecular biology advances, allowing investigators to discover the factors involved in the regeneration process. Factors at the DNA and protein levels have been identified and proven useful in the islet regeneration approach. Both in vivo and in vitro differentiation of non-insulin producing cells into viable islets is a promising area of Type 1 diabetes research. The process of generating islets coupled with preventing recurrent autoimmune attack has the distinct advantage over current insulin therapy because it can potentially reverse the diabetes, not just alleviate its symptoms. The focus of this review will be on recently accepted patents pertaining to regeneration therapy for Type 1 diabetes.     

Insulin action enhancers for the management of Type 2 diabetes mellitus

Type 2 diabetes mellitus is a common metabolic disorder that has become a major public health problem because of the long-term microvascular and macrovascular complications associated with it. Tight glycaemic control has been shown to prevent complications, but a number of studies have shown that many patients with Type 2 diabetes have sub-optimal control. Insulin resistance is a fundamental abnormality in Type 2 diabetes but there have not been drugs that are able to reverse this defect. Thiazolidinediones (TZD) may, therefore, represent a breakthrough in the management of Type 2 diabetes as it is the first class of oral agents for diabetes that act as an insulin action enhancer to reduce insulin resistance. This review will examine available data on the currently available TZDs and consider its place in the management of Type 2 diabetes.     

格列吡嗪盐酸二甲双胍片治疗2型糖尿病的多中心、随机、双盲双模拟临床研究

目的评价格列吡嗪盐酸二甲双胍片(降血糖药)的疗效及安全性。方法用多中心、随机、双盲双模拟临床研究,试验组120例,二甲双胍组、格列吡嗪片组各60例,治疗12周。结果治疗前后试验组较二甲双胍组HbAlc多降低了0.78%,较格列吡嗪组多降低了0.41%(P<0.001);治疗前后试验组较二甲双胍组空腹血糖多降低了0.97 mmol·L~(-1),较格列吡嗪组多降低了1.36 mmol·L~(-1)(P<0.001);低血糖发生率3组相似。结论格列吡嗪盐酸二甲双胍与单药治疗相比,降低HbAlc、空腹及餐后2 h血糖均更为明显,且耐受性很好。     

Orlistat in the treatment of Type 2 diabetes mellitus

The prevalence of Type 2 diabetes mellitus (DM-2) is increasing throughout the world and poses a major public health concern. The majority of patients with DM-2 are overweight or obese and weight loss is generally recommended, both as a first-line therapy and as an adjunct to pharmacological therapies. However, it is generally acknowledged that weight loss, a difficult goal for many overweight and obese individuals, is especially difficult for those with DM-2 and there is interest in whether pharmacological adjuncts may be useful for this purpose. Orlistat is an intestinal lipase inhibitor previously approved for the treatment of obesity. During the past several years, clinical trials have been completed concerning the use of orlistat in the treatment of overweight or obese patients with DM-2. The purpose of this review is to examine the results of these clinical trials. Data on > 2500 orlistat-treated patients with DM-2 are reviewed and summarised. Orlistat therapy led to greater weight loss and improved metabolic control in overweight and obese patients with DM-2.     

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.     

Metformin increases plasma ghrelin in Type 2 diabetes

AIMS

Metformin treatment of Type 2 diabetes is not usually associated with weight gain, and may assist with weight reduction. Plasma ghrelin concentrations are inversely associated with obesity and food intake. Metformin might therefore affect ghrelin concentrations, although previous studies have shown variable results in this regard. The primary aim of this study was to determine the effect of metformin on plasma ghrelin, appetite and satiety in patients with Type 2 diabetes.

METHODS

Eighteen patients with Type 2 diabetes were studied before and after 6 weeks of metformin treatment, which was titrated to 1 g b.d. On the study days patients were fed standard meals of 390 kcal at 08.00 and 12.30 h, plasma samples were collected at 15- and 30-min intervals, and appetite and satiety were measured on visual analogue scales. Changes in the area under the concentration–time curves (AUCs) of plasma ghrelin, insulin, glucose, appetite and satiety were assessed and examined for correlations with metformin AUCs. Changes in fasting adiponectin and leptin were also measured.

RESULTS

Treatment with metformin increased the mean AUC (07.30–16.30 h) of plasma ghrelin by 24% (P= 0.003), while decreasing those of glucose by 19% (P < 0.001) and insulin by 19% (P= 0.001). No changes were detected in hunger and satiety, or in fasting adiponectin or leptin concentrations. There were no clear correlations between metformin plasma concentrations (AUC) and changes in plasma glucose, insulin or ghrelin.

CONCLUSIONS

Treatment of Type 2 diabetes with metformin was associated with increased plasma ghrelin concentrations, without associated changes in hunger and satiety.     

A systematic review of the safety of probiotics

Introduction: Gestational diabetes mellitus (GDM), the most frequent medical complication of pregnancy, is associated with several adverse outcomes over the short- and long-term for both mother and offspring. Standard treatment for GDM consists of insulin injections. Oral hypoglycemic agents (OHAs), on the other hand, are still the subject of controversy. Although OHAs are seemingly as efficient as insulin and may provide better quality of life, congenital malformations and unknown long-term effects are still feared.

Areas covered: Recent data on the pharmacokinetics of two OHAs (glyburide and metformin) and their clinical use for GDM are reviewed, with a focus on clinical trials and observational studies comparing insulin with glyburide or metformin (1960 – 2010). The review will provide a comprehensive overview of the pros and cons of OHA usage, an appreciation of OHAs' efficiency for the purpose of controlling glycemia and embryogenetic basics relating to congenital malformations.

Expert opinion: While insulin treatment is an effective therapy for controlling maternal glycemia, it nevertheless requires sufficient education and skills on the part of the patient to manage properly and may cause hypoglycemia, fear and anxiety. Oral treatment as a more user-friendly alternative may thus facilitate the control of GDM in some patients.     

盐酸二甲双胍缓释片治疗2型糖尿病的临床研究

目的比较二甲双胍缓释片与普通片（降血糖药）的疗效及安全性。方法2型糖尿病患者150例，随机分为2组：对照组（口服普通片）与试验组（口服缓释片）。治疗12周后，以糖化血红蛋白、空腹及餐后2h血糖、胆固醇、低密度脂蛋白、高密度脂蛋白及体质量指数的变化评价二甲双胍缓释片的疗效。结果试验组餐后2h血糖略高于对照组，差异有统计学意义；但2组的2h内血糖曲线下面积非常接近，组间差异无统计学意义。其他实验室检查2组比较无显著性差异。试验过程中，2组药物不良反应发生率分别为8．72％，11．3％。结论二甲双胍缓释片和普通片在为期12周的研究中有相同的降糖、降脂作用，且不良反应轻微。     

Inhaled insulin: recent advances in the therapy of Type 1 and 2 diabetes

There are promising data in the field of inhaled insulin. This article describes the current devices being developed for insulin delivery via inhalation. Encouraging advanced clinical data are available in Type 1 diabetes, where inhaled insulin is used in conjunction with basal insulin. Moreover, patients with Type 2 diabetes who have failed oral therapy show improved control when inhaled insulin therapy is initiated. Safety data show that cough is the most common side effect. Pulmonary function tests have shown some changes in carbon monoxide diffusion in the lung. Further studies are needed to clarify the significance of this finding. Inhaled insulin appears to be a non-invasive, well-tolerated and -liked modality of treatment, with potential in both Type 1 and 2 diabetes.     

比较HMS5552和二甲双胍对2型糖尿病大鼠血糖及肝葡萄糖激酶的调节作用

目的研究二甲双胍对比HMS5552对2型糖尿病大鼠血糖及肝葡萄糖激酶的调节作用。方法以高脂高糖饮食和加一次性注射链脲佐菌素40mg·kg^-1诱导建立2型糖尿病大鼠模型。建模后,实验组大鼠灌胃HMS5552 30mg·kg^-1,对照组灌胃二甲双胍80 mg·kg^-1,正常组和模型组灌胃等体积0.9%Na Cl。连续给药4周,做口服葡萄糖耐量实验后,处死大鼠,心脏采血,检测各项生化指标。用免疫印迹法检测肝葡萄糖激酶(GCK)的蛋白水平。结果给药后,模型组、对照组和实验组在60,90 min血糖浓度分别为(27.27±3.48),(21.47±2.89),(23.67±5.75)mmol·L^-1;(33.30±4.87),(20.72±3.34),(23.13±4.02)mmol·L^-1;这3组的空腹血糖分别为(17.39±1.33),(7.23±0.61),(9.16±1.76)mmol·L^-1;这3组的空腹胰高血糖素分别为(152.85±11.42),(64.76±13.62),(64.64±5.30)mmol·L^-1,对照组和实验组与模型组的上述指标比较,差异均有统计学意义(均P<0.05)。对照组和实验组与模型组的GCK蛋白表达量比较,差异有统计学意义(P<0.05)。结论 HMS5552通过提升GCK的表达来降低血糖并具有改善胰岛β细胞分泌胰岛素的作用。     

The use of orlistat in the treatment of obesity,dyslipidaemia and Type 2 diabetes

Orlistat (tetrahydrolipstatin) is an inhibitor of gastrointestinal lipases, especially pancreatic lipase. It is used as an adjunct to diet and exercise in order to achieve weight loss in obese individuals (body mass index > 30 kg/m²) or in overweight individuals (body mass index > 27 kg/m²) with other risk factors for atherosclerotic vascular disease, such as hypertension, dyslipidaemia or diabetes. Short- and long-term studies of up to 4 years duration have shown the drug to have significant benefits in weight loss, as well as in the reduction in lipids, glucose and haemoglobin A1c, and in time to onset of Type 2 diabetes compared with diet alone or placebo groups. The incremental amount of weight loss that orlistat produces is modest, but sufficient to result in improvement in obesity comorbidities such as elevated blood pressure, dyslipidaemia and hyperglycaemia compared with diet and exercise alone. Orlistat should only be prescribed for individuals who are motivated to adhere to lifestyle modifications, especially dietary fat restriction.