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.     

Tolerability profile of metformin/glibenclamide combination tablets (Glucovance): a new treatment for the management of type 2 diabetes mellitus.

It is important to manage blood glucose intensively in patients with type 2 diabetes mellitus in order to reduce the risk of long-term complications. Oral combination therapy that addresses insulin resistance and beta-cell dysfunction is a proven means of improving glycaemic control when monotherapy becomes insufficiently effective. Metformin/glibenclamide (glyburide) combination tablets were developed to provide a means of applying this strategy while minimising polypharmacy. This review examines the tolerability profile of this treatment from four double-blind, randomised clinical trials in a total of 2342 type 2 diabetic patients with hyperglycaemia despite treatment with diet and exercise, a sulphonylurea or metformin. Treatment with combination tablets was associated with markedly superior blood glucose control, at lower doses of metformin and glibenclamide, compared with monotherapies. The incidence of symptoms of hypoglycaemia varied between dosages and trials, though the incidence of severe or biochemically confirmed hypoglycaemia or withdrawals from clinical trials for this reason was consistently low and comparable with glibenclamide alone. No patient required third-party assistance for hypoglycaemia. Significantly fewer diet-failed patients receiving low-dose combination tablets reported gastrointestinal adverse effects compared with metformin alone, with a comparable incidence between metformin and combination tablets in post-monotherapy studies. The incidence of other adverse events, including serious adverse events, was similar for combination tablets and monotherapies. The lower doses of metformin and glibenclamide with the combination tablet approach, and the design of the combination tablets themselves, may underlie the beneficial tolerability profile of this treatment.     

An evaluation of the therapeutic effects and dosage equivalence of glyburide and glipizide

Nineteen noninsulin-dependent diabetic patients [ten women, nine men, aged 36-80 years (mean +/- SE 56.8 +/- 2.7 years)] were randomized to receive either glyburide or glipizide for 16 weeks, in a double-blind crossover fashion. A 2-week washout period preceded each treatment period. The patients measured blood glucose concentrations 16 times weekly using Chemstrip-bG. The medication dosages were titrated to achieve fasting blood glucose concentrations of less than or equal to 6.2 mM and preprandial and postprandial concentrations of less than or equal to 9.0 mM, or to a total daily dose of 20 mg for glyburide and 40 mg for glipizide. Glyburide therapy resulted in a significant decline in fasting, preprandial, postprandial and bedtime blood glucose levels, while glipizide treatment led to a significant lowering of postprandial and bedtime blood glucose. Furthermore, fasting, preprandial and postprandial blood glucose concentrations were significantly lower during glyburide as compared to glipizide treatment phase. Glycosylated hemoglobin levels were decreased only with glyburide. Serum C-peptide and insulin concentrations were not altered over the entire study. The mean final daily dose of glyburide (15.4 +/- 1.6 mg) was markedly lower than that of glipizide (29.7 +/- 3.1 mg). Thus, in this patient population, glyburide was twice as potent on a weight basis than glipizide.     

Glyburide and glipizide, second-generation oral sulfonylurea hypoglycemic agents

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of glyburide and glipizide, two second-generation oral sulfonylurea hypoglycemic agents, are reviewed. Glyburide and glipizide are well absorbed after oral administration. The absorption of glipizide is delayed by food; in contrast, glyburide absorption does not seem to be affected by administration with meals. Both drugs are extensively metabolized by the liver. A two-compartment open model adequately describes the pharmacokinetics of these drugs. The apparent elimination half-life of glyburide in oral dosage forms available in the United States ranges from 7 to 10 hours. Glipizide has a terminal elimination half-life of 2-7 hours. The effects of renal and hepatic disease on the pharmacokinetics of glyburide and glipizide have not been well studied. Based on controlled, comparative studies in patients with new-onset, diet-failed, Type II diabetes, glyburide appears to be at least as effective as chlorpropamide and tolazamide in controlling blood glucose. Glipizide has shown efficacy comparable to or greater than that of chlorpropamide and tolbutamide. Glyburide and glipizide appear to be comparable in terms of their ability to control fasting blood glucose in Type II diabetics. The recommended initial dosage of glyburide in newly diagnosed Type II diabetics is 2.5-5 mg once daily. For glipizide, the initial dosage should be 5 mg once daily. Elderly or debilitated patients and those with renal or hepatic impairment should be started on lower dosages initially. Glyburide and glipizide have adverse effects that are similar to those observed with the first-generation oral hypoglycemic agents. Glyburide and glipizide do not appear to offer major therapeutic advantages over first-generation oral sulfonylurea hypoglycemic agents. However, they may represent therapeutic alternatives for some patients who do not respond satisfactorily to other sulfonylureas.     

二甲双胍格列吡嗪片治疗2型糖尿病的有效性及安全性的临床研究

目的：以格列吡嗪片和二甲双胍片为对照,评价二甲双胍格列吡嗪片治疗2型糖尿病的有效性和安全性。方法：采用多中心、随机、双盲、三模拟、阳性药平行对照研究方法,用药观察周期为12周,其中试验组服用药物为二甲双胍格列吡嗪片＋格列吡嗪模拟片＋盐酸二甲双胍模拟片;格列吡嗪对照组服用药物为格列吡嗪片＋二甲双胍格列吡嗪模拟片＋盐酸二甲双胍片模拟片;盐酸二甲双胍对照组服用药物为盐酸二甲双胍片＋格列吡嗪模拟片＋二甲双胍格列吡嗪模拟片。结果：随机化入组患者352例,其中二甲双胍格列吡嗪组116例、二甲双胍组118例、格列吡嗪组118例。经治疗12周后,二甲双胍格列吡嗪片组、二甲双胍片组、格列吡嗪片组糖化血红蛋白（HbA1c）分别为（5.5±1.3）%、（6.0±1.4）%、（6.1±1.5）%;空腹血糖分别为（7.3±1.8）、（7.9±2.3）、（8.2±2.4）mmol/L;餐后2小时血糖分别为（11.0±4.0）、（12.2±4.2）、（12.5±4.5）mmol/L,3项指标较用药前均有显著下降,各组疗后组间比较差异有统计学意义（P〈0.05）。治疗后3组餐后2小时胰岛素均有所上升,空腹胰岛素无明显变化。二甲双胍格列吡嗪片、二甲双胍片两组甘油三酯有所下降,格列吡嗪片组有所升高,胆固醇前后差值组间比较无统计学意义。三组共发生不良事件54例,不良反应22例,三组比较无统计学差异。结论：二甲双胍格列吡嗪片是一种安全有效的降糖药物。     

Sitagliptin, an dipeptidyl peptidase-4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects

AIMS

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is an incretin enhancer that is approved for the treatment of Type 2 diabetes. Sitagliptin is mainly renally eliminated and not an inhibitor of CYP450 enzymes in vitro. Glyburide, a sulphonylurea, is an insulin sensitizer and mainly metabolized by CYP2C9. Since both agents may potentially be co-administered, the purpose of this study was to examine the effects of sitagliptin on glyburide pharmacokinetics.

METHODS

In this open-label, randomized, two-period crossover study, eight healthy normoglycaemic subjects, 22–44 years old, received single 1.25-mg doses of glyburide alone in one period and co-administered with sitagliptin on day 5 following a multiple-dose regimen for sitagliptin (200-mg q.d. ×6 days) in the other period.

RESULTS

The geometric mean ratios and 90% confidence intervals [(glyburide + sitagliptin)/glyburide] for AUC_0–∞ and C_max were 1.09 (0.96, 1.24) and 1.01 (0.84, 1.23), respectively.

CONCLUSION

Sitagliptin does not alter the pharmacokinetics of glyburide in healthy subjects.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• No data are available on the potential drug interaction of sitagliptin and glyburide.
• Sitagliptin belongs to a new class of drugs called DPP-4 inhibitors recently approved for the treatment of Type 2 diabetes.

WHAT THIS STUDY ADDS

• Glyburide is a commonly used sulphonylurea medication to treat Type 2 diabetes.
• Combination therapy is often required to achieve adequate glucose control in Type 2 diabetes.
• Sitagliptin does not appear to interfere with glyburide pharmacokinetics and therefore may be potentially co-administered with glyburide for the treatment of Type 2 diabetes.

     

Sulfonylurea treatment of type 2 diabetes mellitus: focus on glimepiride

Sulfonylureas, which have evolved through two generations since their introduction nearly 50 years ago, remain the most frequently prescribed oral agents for treatment of patients with type 2 diabetes mellitus. Glyburide, glipizide, and glimepiride, the newest sulfonylureas, are as effective at lowering plasma glucose concentrations as first-generation agents but are more potent, better tolerated, and associated with a lower risk of adverse effects. Differences in their binding affinity to the beta-cell sulfonylurea receptor have been described, with preservation of cardioprotective responses to ischemia with glimepiride. Clinical studies have shown glimepiride to be safe and effective in reducing fasting and postprandial glucose levels, as well as glycosylated hemoglobin concentrations, with dosages of 1-8 mg/day. In comparative trials, glimepiride was as effective in lowering glucose levels as glyburide and glipizide, but glimepiride was associated with a reduced likelihood of hypoglycemia and a smaller increase in fasting insulin and C-peptide levels than glyburide, and a more rapid lowering of fasting plasma glucose levels than glipizide. Glimepiride also improves first-phase insulin secretion, which plays an important role in reducing postprandial hyperglycemia. Insulin secretagogues, specifically glimepiride, merit consideration as first-line therapy for patients with type 2 diabetes.     

Pharmacokinetics and pharmacodynamics of glyburide/metformin tablets (Glucovance) versus equivalent doses of glyburide and metformin in patients with type 2 diabetes

OBJECTIVE: To compare the effects of two different formulations of glibenclamide (glyburide) combined with metformin on postprandial glucose excursions, and to assess their pharmacokinetics. The formulations were a combination glibenclamide/metformin tablet (Glucovance; controlled-particle-size glibenclamide and metformin) versus glibenclamide (Micronase) and metformin (Glucophage) coadministered separately. DESIGN: A randomised, double-blind, two-way crossover study in which patients with type 2 diabetes received either glibenclamide/metformin 2.5/500mg tablets or glibenclamide 2.5mg with metformin 500mg twice daily for 14 days. After a 2-week washout, patients were crossed over to the other treatment for 14 days. Patients consumed standardised meals on the days when pharmacokinetic and pharmacodynamic evaluations were performed. PARTICIPANTS: Forty patients with type 2 diabetes were enrolled; 37 were randomised (18 men, 19 women) and 35 completed the study. Mean age was 58 years; mean body mass index was 31 kg/m(2). The baseline glycated haemoglobin (HbA(1c)) was 9.3% for both treatment groups. MAIN OUTCOME MEASURE: Two-hour postprandial glucose excursion (PPGE) was used to assess postprandial glucose dynamics. RESULTS: Treatment with glibenclamide/metformin resulted in a significantly smaller mean PPGE than was attained by treatment with glibenclamide plus metformin, according to measurements taken after the day 14 afternoon standardised meal (89.5 vs 117.4 mg/dl, p = 0.011). The mean glibenclamide peak concentration (C(max)) was significantly greater (approximately 16%) after glibenclamide/metformin treatment on both days 1 and 14. Glibenclamide/metformin treatment was associated with a 2-fold greater area under the concentration-time curve to 3 hours for glibenclamide (AUC(3)) [p < 0.001], although the AUC over the administration interval was equivalent for both formulations. CONCLUSION: In patients with type 2 diabetes, glibenclamide/metformin resulted in lower PPGE, suggesting that the higher glibenclamide AUC(3) observed with this formulation may contribute to better postprandial glycaemic control than is attained by glibenclamide plus metformin separately.     

Vildagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus

Introduction:

Type 2 diabetes is increasing in prevalence worldwide and is a leading cause of morbidity and mortality, mainly due to the development of complications. Vildagliptin is an inhibitor of dipeptidyl peptidase 4 (DPP-4), a new class of oral antidiabetic agents.

Aims:

To evaluate the role of vildagliptin in the management of type 2 diabetes.

Evidence review:

Clear evidence shows that vildagliptin improves glycemic control (measured by glycosylated hemoglobin and blood glucose levels) more than placebo in adults with type 2 diabetes, either as monotherapy or in combination with metformin. Vildagliptin is as effective as pioglitazone and rosiglitazone, and slightly less effective than metformin, although better tolerated. Further glycemic control is achieved when adding vildagliptin to metformin, pioglitazone, or glimepride. There is evidence that vildagliptin improves beta-cell function and insulin sensitivity. Vildagliptin does not appear to be associated with weight gain or with a higher risk of hypoglycemia than placebo or other commonly used oral antidiabetic agents. Economic evidence is currently lacking.

Place in therapy:

Vildagliptin improves glycemic control with little if any weight gain or hypoglycemia in adult patients with type 2 diabetes when given alone or in combination with metformin, thiazolidinediones, or sulfonylureas. Since many diabetic patients require combination therapy, the complementary mechanism of action of vildagliptin and other commonly prescribed antidiabetic drugs represents an important new therapeutic option in diabetes management.     

Type 2 diabetes in pediatrics and adults: thoughts from a clinical pharmacology perspective

Type 2 diabetes results when insulin secretion is unable to keep the plasma glucose levels as per acceptable range. This leads to chronic hyperglycemia and its associated microvascular complications such as renal impairment (diabetic nephropathy), retinal abnormalities (diabetic retinopathy), and autonomic, sensory, and motor neuropathies (diabetic neuropathy) and macrovascular disease. Historically, type 2 diabetes is well known as an adult-onset disease; however, lately, the incidence of the disease is reported to be increasing in children. Despite the wealth of information concerning type 2 diabetes in adults, data unique to the pediatric age group regarding the pathophysiology and therapy for type 2 diabetes are limited. For treatment in pediatric type 2 diabetes, metformin and insulin are the only antidiabetic agents approved currently. There are data of use of other oral antidiabetic drugs including glimepiride, rosiglitazone, and glyburide (in combination with metformin) in pediatric patients; however, formal clinical trials to establish the safety and efficacy have not been conducted. This review will compare the clinical pharmacology aspects of the oral type 2 diabetic drugs in pediatric and adult populations in order to determine any differences between the two patient groups.     

Evaluation of pharmacokinetic and pharmacodynamic interaction between the dipeptidyl peptidase IV inhibitor vildagliptin, glyburide and pioglitazone in patients with Type 2 diabetes

Background: Vildagliptin is a selective inhibitor of dipeptidyl peptidase IV (DPP-4) that improves glycemic control and pancreatic b-cell function in patients with Type 2 diabetes. Vildagliptin may be an appropriate agent to combine with other antihyperglycemic agents in patients requiring combination therapy to achieve optimal glycemic control. Two studies were performed to determine the potential for pharmacokinetic and pharmacodynamic interactions between vildagliptin and the sulfonylurea, glyburide, or pioglitazone in patients with Type 2 diabetes. Methods: Two open-label, multiple-dose, 3-period, randomized, crossover studies in patients with Type 2 diabetes were carried out. Steady state drug pharmacokinetics and postprandial plasma glucose and insulin responses were assessed during treatment with vildagliptin 100 mg b.i.d. alone and in combination with glyburide 10 mg q.d. (n = 17) or with vildagliptin 100 mg q.d. alone or in combination with pioglitazone 45 mg q.d. (n = 15). Results: Coadministration of vildagliptin with either glyburide or pioglitazone had no clinically significant effect on the pharmacokinetics of any of the 3 drugs. Changes in AUC and Cmax during combination treatment were small ( pound 15%), and 90% confidence intervals for the geometric mean ratios (drug coadministration/monotherapy) were generally contained within the acceptance range for bioequivalence (0.80 - 1.25). Vildagliptin/glyburide coadministration significantly reduced the area under the plasma glucose-time curve compared with glyburide alone (AUE0-5h reduced by 12% (p = 0.005) and AUE0-15h by 13% (p = 0.003)), and increased the area under the plasma insulin-time curve (AUE0-15h increased by 12% (p = 0.041)). Vildagliptin/pioglitazone coadministration also significantly reduced postprandial glucose exposure compared with pioglitazone alone (AUE0.5-5.5h reduced by 11% (p = 0.029) and AUE0-15.5h by 10% (p = 0.019)). Vildagliptin was generally well tolerated whether administered alone or in combination with glyburide or pioglitazone, and was not associated with hypoglycemia. Conclusions: Coadministration of vildagliptin with either glyburide or pioglitazone in patients with Type 2 diabetes improves postprandial glycemic control without notable effects on drug pharmacokinetics.     

联合沙格列汀与二甲双胍治疗2型糖尿病的临床疗效分析

目的探讨二甲双胍联合沙格列汀治疗2型糖尿病效果。方法96例糖尿病患者随机分为二甲双胍组、联合用药组各48例,二甲双胍组给二甲双胍,0.5 g,tid,po;联合用药组另加沙格列汀片,5mg,qd,po。结果治疗6个月以后,联合用药组空腹血糖(FBG)(6.01±0.97)mol/L、餐后2 h血糖(2hPBG)(8.53±1.22)mol/L、糖化血红蛋白HbAlc(6.94±0.88)%、体重指数(BMI)(24.47±1.09)kg/m^2低于二甲双胍组的(7.42±1.04)mol/L、(9.28±1.34)mol/L、(7.14±0.97)%、(25.82±1.22)kg/m^2(P<0.05);总有效率95.83%高于二甲双胍组83.33%(P<0.05)。结论联合沙格列汀与二甲双胍治疗2型糖尿病,显著降低FBG、2hPBG、HbAlc、BMI,提高治疗总有效率。     

First approved inhaled insulin therapy for diabetes mellitus

The long-term benefits of tight glycemic control in preventing microvascular and macrovascular complications are well established in both Type 1 diabetes mellitus (Type 1 DM) and Type 2 diabetes mellitus (Type 2 DM). Nonetheless, achievement of recommended haemoglobin A1c (HbA(1c)) goals (< or = 6.5 - 7.0%) has remained elusive, especially in patients with diabetes who require insulin therapy. Delayed/suboptimal titration of insulin is partly related to poor acceptance of multiple injection regimen by both physicians and patients. EXUBERA (human insulin [rDNA origin]; Pfizer), the first approved inhaled insulin for the treatment of diabetic patients, has been shown to be safe and as effective as regular/rapidly acting insulin in improving glycemic control. In addition to controlling postprandial glucose excursions, EXUBERA exerts a major action to reduce fasting plasma glucose (FPG) concentration. Thus, it has the potential to be used as a monotherapy in Type 2 DM, as well as in combination with an insulin sensitizer in Type 2 DM or in combination with long-acting insulin in both Type 2 DM and Type 1 DM.     

The development of an oral antidiabetic combination tablet: design,evaluation and clinical benefits for patients with type 2 diabetes

Type 2 diabetes is a chronic and progressive disease. Oral antidiabetic monotherapies directly address only one defect as their primary mechanism of action, and do not control blood glucose sufficiently well to meet current glycaemic targets. In consequence, most patients need combination therapy within a few years. However, the co-administration of two or more oral antidiabetic drugs may render treatment regimens difficult to follow. Combining oral antidiabetic agents into a single tablet provides a means of intensifying antidiabetic therapy while supporting good patient compliance. An insulin sensitiser and an insulin secretagogue represent a rational oral antidiabetic combination, as they address the dual endocrine defects of insulin resistance and impaired beta-cell function in type 2 diabetes. Nevertheless, the components of a combination tablet must be carefully chosen. Metformin (an insulin sensitiser) and glibenclamide (an insulin secretagogue) are well supported by decades of clinical evidence, and the pharmacokinetics of these agents support twice-daily co-administration. The final technical challenge is to optimise their delivery within a single-tablet combination. A recently-introduced metformin-glibenclamide combination tablet (Glucovance) has been extensively studied in well-designed clinical trials, where it has been shown to be more effective than its component monotherapies in controlling fasting and postprandial glycaemia. This treatment provides a case study in the development of a single-tablet oral antidiabetic combination, in terms of the pharmacokinetic issues facing the development of this preparation, and the implications of the pharmacokinetic properties of the components of the combination tablet on their pharmacodynamic actions and risk-benefit profile.     

Clinical review of glimepiride

This article reviews the pharmacological and clinical aspects of glimepiride, the latest second-generation sulfonylurea for treatment of Type 2 diabetes mellitus (DM). Glimepiride therapy ameliorates the relative insulin secretory deficit found in most patients with Type 2 DM. It is a direct insulin secretagogue; indirectly, it also increases insulin secretion in response to fuels such as glucose. Its action to augment insulin secretion requires binding to a high affinity sulfonylurea receptor, which results in closure of ATP-sensitive potassium channels in the β-cells of the pancreas. The question has been raised whether insulin secretagogues by acting on vascular or myocardial potassium channels may prevent ischaemic preconditioning, a physiological adaptation that could affect the outcome of coronary heart disease, but there is evidence against this concern being applicable to glimepiride. Glimepiride’s antihyperglycaemic efficacy is equal to other secretagogues. It has pharmacokinetic properties that make it less prone to cause hypoglycaemia in renal dysfunction than some other insulin secretagogues, particularly glyburide (also known as glibenclamide in Europe). Its convenient once daily dosing may enhance compliance for diabetic patients who often also require medications for other co-morbid conditions, such as hypertension, hyperlipidaemia and cardiac disease. Glimepiride is approved for monotherapy, for combination with metformin and with insulin. Clinically, its reduced risk of hypoglycaemia makes it preferable to some other insulin secretagogues when attempting to achieve recommended glycaemic control (haemoglobin A_1c (HgbA_1c) 7%). Using suppertime neutral protamine Hagedorn (NPH) and regular insulin with morning glimepiride in overweight diabetic patients achieves glycaemic goals more quickly than insulin alone and with lower insulin doses.     

Clinical review of glimepiride

This article reviews the pharmacological and clinical aspects of glimepiride, the latest second-generation sulfonylurea for treatment of Type 2 diabetes mellitus (DM). Glimepiride therapy ameliorates the relative insulin secretory deficit found in most patients with Type 2 DM. It is a direct insulin secretagogue; indirectly, it also increases insulin secretion in response to fuels such as glucose. Its action to augment insulin secretion requires binding to a high affinity sulfonylurea receptor, which results in closure of ATP-sensitive potassium channels in the beta-cells of the pancreas. The question has been raised whether insulin secretagogues by acting on vascular or myocardial potassium channels may prevent ischaemic preconditioning, a physiological adaptation that could affect the outcome of coronary heart disease, but there is evidence against this concern being applicable to glimepiride. Glimepiride's antihyperglycaemic efficacy is equal to other secretagogues. It has pharmacokinetic properties that make it less prone to cause hypoglycaemia in renal dysfunction than some other insulin secretagogues, particularly glyburide (also known as glibenclamide in Europe). Its convenient once daily dosing may enhance compliance for diabetic patients who often also require medications for other co-morbid conditions, such as hypertension, hyperlipidaemia and cardiac disease. Glimepiride is approved for monotherapy, for combination with metformin and with insulin. Clinically, its reduced risk of hypoglycaemia makes it preferable to some other insulin secretagogues when attempting to achieve recommended glycaemic control (haemoglobin A(1c) (HgbA(1c)) 7%). Using suppertime neutral protamine Hagedorn (NPH) and regular insulin with morning glimepiride in overweight diabetic patients achieves glycaemic goals more quickly than insulin alone and with lower insulin doses.     

用不同剂型二甲双胍治疗2型糖尿病合并肺癌的药物经济学评价

目的：对二甲双胍缓释片（商品名美哒灵）和二甲双胍片（商品名格华止）治疗2型糖尿病合并肺癌进行药物经济学评价,为临床合理用药提供参考。方法：将60例2型糖尿病合并肺癌病人随机分为A组和B组,分别给予二甲双胍缓释片和二甲双胍片治疗,进行12周的疗效观察,做成本-效果比分析,并统计药品不良反应（ADRs）发生情况。结果：两组病人均能达到理想的血糖控制效果,治疗前后空腹血糖、餐后2h血糖和糖化血红蛋白变化量无明显组间差异。A组的成本-效果比明显低于B组,但B组的ADRs发生率更低（P〈0.01）。结论：二甲双胍缓释片治疗2型糖尿病合并肺癌的成本-效果比优于二甲双胍片。     

Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus

Repaglinide (Prandin), NovoNorm, GlucoNorm, an oral insulin secretagogue, was the first meglitinide analogue to become available for use in patients with type 2 diabetes mellitus. The drug lowers postprandial glucose excursions by targeting early-phase insulin release, an effect thought to be important in reducing long-term cardiovascular complications of diabetes. Repaglinide provided similar overall glycaemic control to that achieved with glibenclamide (glyburide), as assessed by glycosylated haemoglobin (HbA(1c)) and fasting blood glucose levels, and was generally well tolerated in well designed clinical trials. Its rapid onset and relatively short duration of action allow for flexible meal schedules. Two modelled US cost-effectiveness analyses projected lifetime costs and outcomes for a hypothetical cohort of patients with type 2 diabetes. Both analyses projected long-term complications using data on HbA(1c) level changes from short-term clinical trials. Repaglinide plus rosiglitazone was dominant over rosiglitazone in one analysis, and repaglinide plus metformin was dominant over nateglinide plus metformin in the other. A similar Canadian analysis showed a favourable incremental cost-effectiveness ratio (相似文献   

Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus

Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a new class of oral antidiabetic agents designed to normalise postprandial glucose excursions in patients with type 2 diabetes mellitus. Like the sulphonylureas, repaglinide reduces blood glucose by stimulating insulin release from pancreatic beta-cells, but differs from these and other antidiabetic agents in its structure, binding profile, duration of action and mode of excretion. In clinical trials of up to 1-year's duration, repaglinide maintained or improved glycaemic control in patients with type 2 diabetes mellitus. In comparative, 1-year, double-blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to 4mg before 3 daily meals) achieved similar glycaemic control to that in patients receiving glibenclamide (glyburide) < or = 15 mg/day and greater control than patients receiving glipizide < or = 15 mg/day. Changes from baseline in glycosylated haemoglobin and fasting blood glucose levels were similar between patients receiving repaglinide and glibenclamide in all studies; however, repaglinide was slightly better than glibenclamide in reducing postprandial blood glucose in I short term study (n = 192). Patients can vary their meal timetable with repaglinide: the glucose-lowering efficacy of repaglinide was similar for patients consuming 2, 3 or 4 meals a day. Repaglinide showed additive effects when used in combination with other oral antidiabetic agents including metformin, troglitazone, rosiglitazone and pioglitazone, and intermediate-acting insulin (NPH) given at bedtime. In 1-year trials, the most common adverse events reported in repaglinide recipients (n = 1,228) were hypoglycaemia (16%), upper respiratory tract infection (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The overall incidence of hypoglycaemia was similar to that recorded in patients receiving glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the incidence of serious hypoglycaemia appears to be slightly higher in sulphonylurea recipients. Unlike glibenclamide, the risk of hypoglycaemia in patients receiving repaglinide was not increased when a meal was missed in 1 trial. In conclusion, repaglinide is a useful addition to the other currently available treatments for type 2 diabetes mellitus. Preprandial repaglinide has displayed antihyperglycaemic efficacy at least equal to that of various sulphonylureas and is associated with a reduced risk of serious hypoglycaemia. It is well tolerated in a wide range of patients, including the elderly, even if a meal is missed. Furthermore, glycaemic control is improved when repaglinide is used in combination with metformin. Thus, repaglinide should be considered for use in any patient with type 2 diabetes mellitus whose blood glucose cannot be controlled by diet or exercise alone, or as an adjunct in patients whose glucose levels are inadequately controlled on metformin alone.     

Effect of the sulfonylurea glyburide on glutathione and glutathione peroxidase activity in alloxan-induced diabetic rat hepatocytes

1. The effect of glyburide treatment on glutathione peroxidase activity and glutathione levels of non-insulin diabetic rats has been studied.2. Hepatic glutathione and glutathione peroxidase concentrations were significantly reduced in diabetic animals.3. Glyburide treatment of diabetic rats for 4 weeks corrected the changes on the glutathione levels observed in diabetic liver.4. High blood glucose levels of untreated diabetic rats were decreased following glyburide treatment as well.5. Administration of glyburide to diabetic rats reversed the diabetes-induced changes suggesting that glyburide may directly increase liver glutathione concentrations.