Treating type 2 diabetes in renal insufficiency: the role of pioglitazone

The advent of new antidiabetic drugs is of special importance for diabetic patients with already impaired renal function since renal insufficiency is a relative or absolute contraindication for several of the established hypoglycemic drugs. Pioglitazone is a novel oral hypoglycemic agent that increases insulin responsiveness in target tissues. Pioglitazone and its active metabolites are excreted mainly via the liver. Drug exposure remains almost constant across a wide range of renal function since there is no accumulation of the drug or its active metabolites during repeated dosing in renal insufficiency. The pharmacokinetic properties of pioglitazone are ideally suited for patients with renal insufficiency. Although there are possible side effects (mainly fluid retention and weight gain and--very rarely--hepatotoxicity). Pioglitazone has a good safety profile in diabetic patients with impaired renal function.     

胰岛素联合吡格列酮治疗2型糖尿病

将60例新诊断的T2DM患者随机分成2组；胰岛素组30例，胰岛素＋吡格列酮组30例。观察12周。在开始和结束时测定空腹血糖、和糖化血红蛋白，记录胰岛素用量和低血糖情况。胰岛素＋吡格列酮组胰岛素用量比胰岛素组减少20％[（38．2±9．5）u／d，vs（48．0±10．8）u／d，P〈0．05]，HbA1c水平和低血糖发生次数亦均低于胰岛素组（P〈0．05）。     

Combination therapy for patients with uncontrolled type 2 diabetes mellitus: adding empagliflozin to pioglitazone or pioglitazone plus metformin

Introduction: For patients with type 2 diabetes mellitus (T2DM), there is a growing interest in sodium glucose co-transporter 2 (SGLT2) inhibitors, a class of glucose-lowering agents that act independently of insulin secretion and insulin action and also have a weight-lowering effect. Empagliflozin is an SGLT2 inhibitor that has been demonstrated to significantly reduce blood glucose levels and is well tolerated in patients with T2DM.

Areas covered: Kovacs et al. have reported a randomized, placebo-controlled study of empagliflozin as add-on to pioglitazone or pioglitazone plus metformin in patients with T2DM. The study results are evaluated, and potential impact on clinical practice is considered.

Expert opinion: The addition of empagliflozin to pioglitazone or pioglitazone plus metformin treatment may offer some advantages. Together, their complementary mechanisms of action result in significant reductions in glycated hemoglobin levels, weight, and blood pressure, with a low risk of hypoglycemia, but were associated with an increased risk of events consistent with genital mycotic infections.     

New approaches to treating type 2 diabetes mellitus in the elderly: role of incretin therapies

The increasing proportion of elderly persons in the global population, and the implications of this trend in terms of increasing rates of chronic diseases such as type 2 diabetes mellitus, continue to be a cause for concern for clinicians and healthcare policy makers. The diagnosis and treatment of type 2 diabetes in the elderly is challenging, as age-related changes alter the clinical presentation of diabetic symptoms. Once type 2 diabetes is diagnosed, the principles of its management are similar to those in younger patients, but with special considerations linked to the increased prevalence of co-morbidities and relative inability to tolerate the adverse effects of medication and hypoglycaemia. In addition, there are many underappreciated factors complicating diabetes care in the elderly, including cognitive disorders, physical disability and geriatric syndromes, such as frailty, urinary incontinence and pain. Available oral antihyperglycaemic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors and thiazolidinediones. Unfortunately, as type 2 diabetes progresses in older persons, polypharmacy intensification is required to achieve adequate glycaemic control with the attendant increased risk of adverse effects as a result of age-related changes in drug metabolism. The recent introduction of the incretins, a group of intestinal peptides that enhance insulin secretion after ingestion of food, as novel oral antihyperglycaemic treatments may prove significant in older persons. The two main categories of incretin therapy currently available are: glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). The present review discusses the effect of aging on metabolic control in elderly patients with type 2 diabetes, the current treatments used to treat this population and some of the more recent advances in the field of geriatric type 2 diabetes. In particular, we highlight the efficacy and safety of GLP-1 and DPP-4 inhibitors, administered as monotherapy or in combination with other oral antihyperglycaemic agents, especially when the relevant clinical trials included older persons. There is strong evidence that use of incretin therapy, in particular, the DPP-4 inhibitors, could offer significant advantages in older persons. Clinical evidence suggests that the DPP-4 inhibitors vildagliptin and sitagliptin are particularly suitable for frail and debilitated elderly patients because of their excellent tolerability profiles. Importantly, these agents lack the gastrointestinal effects seen with metformin and alpha-glucosidase inhibitors taken alone, and have a low risk of the hypoglycaemic events commonly seen with agents that directly lower blood glucose levels.     

Review of approved pioglitazone combinations for type 2 diabetes

INTRODUCTION: Pioglitazone is approved in combination with several other blood-glucose-lowering drugs for the treatment of type 2 diabetes mellitus (T2DM). Beyond lowering blood glucose levels, each combination of different blood-glucose-lowering drugs for the treatment of T2DM evolves specific pleiotropic effects, which might be considered on an individual basis in a certain patient. AREAS COVERED: The objective of this article is to provide a short review of the pathophysiology of T2DM and to provide a rationale for the combination of pioglitazone with other antidiabetic drugs, based on a pathophysiological understanding of T2DM. Therefore, a PubMed search was undertaken covering the search terms 'pioglitazone', 'antidiabetic drugs' and 'combination therapy'. EXPERT OPINION: Treatment with pioglitazone in T2DM was shown to improve insulin resistance and blood glucose levels without increasing the risk of hypoglycemia. Beyond those metabolic activities, pioglitazone was shown to evolve anti-inflammatory and anti-atherogenic effects. It seems useful to combine different antidiabetic drugs based on the specific needs and contraindications in an individual patient. The treating of T2DM patients by addressing not only glucose control, but also the underlying pathophysiological etiology might help to improve patient prognosis in the long run, especially with regard to the vascular complications.     

吡格列酮治疗2型糖尿病的双盲、随机、平行对照多中心临床研究

目的 :观察吡格列酮对 2型糖尿病病人血糖控制的疗效和安全性。方法 :多中心、随机双盲、安慰剂平行对照的为期 12wk试验。吡格列酮组12 0例 ,安慰剂组 12 0例。结果 :吡格列酮组空腹和餐后 2h血糖治疗后较前皆明显下降 :(1.5±s1.8)mmol·L- 1和 (2 .2± 2 .8)mmol·L- 1(P <0 .0 1) ,糖化血红蛋白从 (7.5± 1.2 ) %下降至 (6 .7± 1.3) %。而安慰剂组则从 (7.3± 1.4 ) %上升至(7.6± 1.2 ) % ,2组间存在非常显著差异 (P <0 .0 1)。但 2组治疗前后的空腹及餐后 2h胰岛素变化无显著差异 (P >0 .0 5 )。吡格列酮组的HDL明显高于安慰剂组 (P <0 .0 5 ) ,而TG/HDL比值则无显著差异 (P >0 .0 5 )。吡格列酮组和安慰剂组的不良反应发生率分别为 6 .0 %和 4 .4 % ,2组间无显著差异 (P >0 .0 5 )。结论 :吡格列酮有良好的降糖作用 ,还可改善脂代谢 ,而且不良反应较低     

Fixed-dose combination therapy for type 2 diabetes: sitagliptin plus pioglitazone

Importance of the field: Type 2 diabetes is typically associated with insulin resistance and dysfunction of insulin-secreting pancreatic beta-cells. Addressing these defects often requires therapy with a combination of differently acting antidiabetic agents. A potential novel combination in development brings together the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin with the thiazolidinedione pioglitazone into a fixed-dose single-tablet combination. The former component acts mainly to increase prandial insulin secretion; the latter improves insulin sensitivity.

Areas covered in this review: To date, clinical trials conducted in type 2 diabetes patients have used combinations of sitagliptin (100 mg/day) and pioglitazone (30 – 45 mg/day) as separate tablets. These trials have shown that the combinations offer additive efficacy in reducing blood glucose when given as initial antidiabetic therapy and as add-on therapy when pioglitazone alone fails to maintain glycemic control.

What the reader will gain: Initial therapy with a combination of sitagliptin (100 mg/day) and pioglitazone (30 mg/day) reduced HbA1c by > 2% starting from a baseline > 9%. Adding sitagliptin (50 – 100 mg/day) to patients inadequately controlled on pioglitazone reduced HbA1c by 0.7 – 1.4% from a baseline of 8 – 8.5%. The combination did not increase the risk of hypoglycemia and produced similar or slightly more weight gain than pioglitazone alone when introduced as initial antidiabetic therapy.

Take home message: The combination of sitagliptin and pioglitazone was well tolerated in these trials, and would appear to be suited to a fixed-dose single-tablet combination for once-daily administration.     

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.     

吡格列酮治疗2型糖尿病合并代谢综合征的临床疗效观察

目的观察吡格列酮治疗2型糖尿病合并代谢综合征的临床疗效。方法选择68例患者随机分为研究组与对照组,各34例。两组患者均应用二甲双胍进行治疗,部分患者根据病情合用格列美脲,同时采用饮食、运动控制治疗。研究组则在上述基础治疗上加用吡格列酮30mgQd。结果研究组随访6个月时的HbA1c水平明显低于对照组（P〈0．05）HOMA—IR在随访3个月和6个月时研究组均明显低于对照组（P〈0．05）研究组HDL—c在随访3个月和6个月时均明显高于基线水平垆〈0．05）研究组DBP在随访6个月时明显低于对照组垆〈0．05）。结论吡格列酮可同时干预MS的多个指标,从而提高2型糖尿病合并代谢综合征的治疗效果。     

吡格列酮联合二甲双胍治疗2型糖尿病效果的meta分析

目的：系统评价吡格列酮联合二甲双胍治疗2型糖尿病的疗效和安全性。方法：检索Cochrane Library、PubMed、EMbase、CBM、CNKI、VIP、WanFang Data共7个数据库,收集主题为吡格列酮联合二甲双胍治疗2型糖尿病的文献;根据排除标准筛选确定最终文献,并根据Cochrane手册评价纳入研究质量,最后提取结局指标数据运用RevMan 5.2进行meta分析。结果：纳入15篇文献,包含T2DM患者1881例,其中联合组941例,二甲双胍单用组940例。结果显示,联合组更能有效降低血糖和糖化血红蛋白,改善胰岛素及血脂,但体质指数无显著差异;不良反应方面,两组在胃肠道事件发生率方面无显著差异;但联合组的水肿发生率略高于单用组。结论：联合用药效果优于二甲双胍单用,且安全性良好。     

Lixisenatide for type 2 diabetes mellitus

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is an increasing health problem worldwide. Glucagon-like peptide-1 (GLP-1) receptor agonists are an expanding drug class that target several of the pathophysiological traits of T2DM. Lixisenatide is a GLP-1 receptor agonist in development for once-daily treatment of T2DM. AREAS COVERED: Pharmacological, preclinical and clinical evidence demonstrating the applicability of lixisenatide for the treatment of T2DM are reviewed. Available data and pending clinical development are summarized, critically appraised and compared to competitor drugs. The most relevant papers and meeting abstracts published up to November 2010 are used as sources for this review. EXPERT OPINION: Efficacy and safety in T2DM are demonstrated with lixisenatide in monotherapy and in combination with metformin. However, limited data with the intended once-daily 20 μg subcutaneous dosing necessitate further evaluation of lixisenatide as add-on to various antidiabetic treatments. It remains to be established whether the slightly differing chemical properties compared to other GLP-1 receptor agonists including a rather short duration of action will be a disadvantage or maybe even an advantage, for example, when combined with long-acting insulin.     

Long-term safety of pioglitazone versus glyburide in patients with recently diagnosed type 2 diabetes mellitus

STUDY OBJECTIVE: To evaluate the long-term safety and efficacy of glyburide versus pioglitazone in patients with a recent diagnosis of type 2 diabetes mellitus. DESIGN: Prospective, randomized, multicenter, double-blind trial with a 16-week titration period and a 40-week maintenance period. SETTING: Sixty-five investigative sites in the United States and Puerto Rico. PATIENTS: Five hundred two subjects with a recent diagnosis of type 2 diabetes that was unsuccessfully treated with diet and exercise were randomly assigned to study treatment. Of the 251 patients in each treatment group, 128 (51.0%) glyburide-treated patients and 134 (53.4%) pioglitazone-treated patients completed the study. INTERVENTIONS: Dosages of randomly assigned glyburide and pioglitazone were titrated every 4 weeks for 16 weeks in 5-mg/day and 15-mg/day increments, respectively, until a fasting plasma glucose level between 69 and 141 mg/dl was achieved. The optimized regimen was maintained during the subsequent 40-week double-blind phase. MEASUREMENTS AND MAIN RESULTS: At week 56, glyburide and pioglitazone improved glucose control comparably (change in hemoglobin A(1c) -2.02% and -2.07%, respectively, p=0.669). Withdrawal due to lack of efficacy or adverse events occurred more frequently with glyburide (20.8%) than pioglitazone (12.8%, p<0.032). Significantly higher percentages of glyburide- than pioglitazone-treated patients had a hypoglycemic (24.3% vs 4.4%, p=0.0001) or cardiac (8.8% vs 4.4%, p=0.0478) event. Edema (4.8% vs 7.9%, p=0.1443) and weight gain (4.4% vs 4.0%, p=0.8238) did not differ significantly between the glyburide and pioglitazone groups. Only a few patients discontinued study drug because of weight gain (one glyburide, one pioglitazone), edema (one pioglitazone), or a cardiac event (two glyburide). CONCLUSION: With long-term treatment, both glyburide and pioglitazone resulted in comparable glycemic control; however, pioglitazone was associated with less hypoglycemia and fewer withdrawals due to lack of efficacy or adverse events.     

Implications of rosiglitazone and pioglitazone on cardiovascular risk in patients with type 2 diabetes mellitus

Clinical data suggest that thiazolidinediones--specifically, rosiglitazone and pioglitazone--may improve cardiovascular risk factors through multiple mechanisms. Low insulin sensitivity has been described as an independent risk factor for coronary artery disease and cerebrovascular disease. Patients with insulin resistance often have several known risk factors, such as obesity, dyslipidemia, and hypertension. Other emerging risk factors may be prevalent in patients with insulin resistance, such as hyperinsulinemia, elevated C-reactive protein, elevated plasminogen activator inhibitor levels, and small, dense, low-density lipoproteins. The only available drug class that primarily targets insulin resistance is the thiazolidinediones. These drugs have shown efficacy in affecting surrogate markers of cardiovascular risk in patients with diabetes mellitus. Alterations in these risk factors are likely due to their effects on improving insulin sensitivity and/or glycemic control. Trials to assess whether thiazolidinediones actually reduce cardiovascular outcomes are continuing.     

糖尿乐胶囊联合吡格列酮治疗2型糖尿病的临床研究

目的 探讨糖尿乐胶囊联合盐酸吡格列酮片治疗2型糖尿病的临床疗效。方法 选取2020年4月—2023年3月华北医疗健康集团峰峰总医院收治的100例2型糖尿病患者,将100例患者随机分为对照组（50例）和治疗组（50例）。对照组患者口服盐酸吡格列酮片,2片/次,1次/d。治疗组患者在对照组患者的基础上口服糖尿乐胶囊,4粒/次,3次/d。两组患者持续治疗3个月。比较两组临床效果、临床症状消失时间、血糖指标和血清指标。结果 治疗后,治疗组的总有效率为94.00%,对照组的总有效率为78.00%,组间差异显著（P＜0.05）。治疗后,治疗组多饮、多尿、乏力消失时间均明显短于对照组（P＜0.05）。治疗后,两组的空腹血糖（FPG）、餐后血糖（PPG）、糖化血红蛋白（HbA1c）均低于治疗前（P＜0.05）,且治疗组血糖指标较对照组更低（P＜0.05）。治疗后,两组的血清中性粒细胞与淋巴细胞比率（NLR）、血清肾损伤分子-1（KIM-1）、中性粒细胞明胶酶相关载脂蛋白（NGAL）水平低于治疗前（P＜0.05）;治疗组的血清NLR、KIM-1、NGAL水平低于对照组（P＜0.05）。结论 糖尿乐胶囊联合盐酸吡格列酮片可提高2型糖尿病的疗效,促进症状好转,进一步降低血糖,有助于降低肾损伤。     

Cost effectiveness of combination therapy with pioglitazone for type 2 diabetes mellitus from a german statutory healthcare perspective

BACKGROUND: Pioglitazone has been approved in Europe for oral combination therapy for type 2 diabetes mellitus. Along with other agents of the thiazolidinedione class, it has a novel intracellular mechanism of action. Clinical trials with pioglitazone have confirmed a strong product profile in terms of control of blood glucose and lipids. However, the drug acquisition cost for pioglitazone is greater than standard medications for type 2 diabetes. Long-term data regarding the cost effectiveness of pioglitazone-based combination therapy are not available. OBJECTIVE: To evaluate, using a decision analysis model, the cost effectiveness of pioglitazone-based combination therapy compared with relevant alternative medications for the treatment of type 2 diabetes in Germany. METHODS: This study compared the clinical effects and costs of pioglitazone 30 mg added to metformin in patients who failed metformin monotherapy and pioglitazone added to a sulphonylurea in patients who failed sulphonylurea monotherapy, with the most relevant treatment alternatives. A published and validated Markov model was adapted to reflect the management of type 2 diabetes. This simulated the number of severe complications occurring and the mean life expectancy of a diabetic cohort, which was based on the overweight group of the UK Prospective Diabetes Study at year 6 of follow-up. Drug treatment costs, other costs for general management of type 2 diabetes and the costs of complications were combined to compute overall lifetime treatment costs from the perspective of the German statutory healthcare system in 2002. RESULTS: Combination therapy with pioglitazone/metformin was associated with a higher life expectancy (15.2 years) relative to sulphonylurea/metformin (14.9 years) or acarbose/metformin (14.7 years). Likewise, pioglitazone/sulphonylurea (15.5 years) was superior to metformin/sulphonylurea (14.9 years) and acarbose/sulphonylurea (14.8 years). Undiscounted incremental cost-effectiveness ratios in comparison to the next best strategy were euro20,002 per life-year gained (LYG) for pioglitazone/metformin versus sulphonylurea/metformin, and euro8707 per LYG for pioglitazone/sulphonylurea versus metformin/sulphonylurea. After discounting costs and life expectancy at 5% per year, the incremental cost-effectiveness ratio was euro47 636 per LYG for pioglitazone/metformin versus sulphonylurea/metformin, and euro19 745 per LYG for pioglitazone/sulphonylurea versus metformin/sulphonylurea. CONCLUSIONS: In this model, with its underlying assumptions and data, combination therapy with pioglitazone increased life expectancy in overweight type 2 diabetes patients at acceptable cost compared with other well established medications in Germany. These findings should be re-evaluated as soon as additional evidence becomes available from the currently ongoing long-term clinical and economic studies.     

A lifetime modelled economic evaluation comparing pioglitazone and rosiglitazone for the treatment of type 2 diabetes mellitus in the UK

INTRODUCTION: Adding pioglitazone or rosiglitazone to existing therapy are alternative treatment options for patients with type 2 diabetes mellitus who have insufficient glycaemic control while receiving the maximal tolerated dose of metformin monotherapy. Our objective was to develop a lifetime model of type 2 diabetes mellitus and its sequelae in order to compare the costs and benefits of pioglitazone versus rosiglitazone in combination with metformin. METHODS: A decision-analytic model employing a first order Monte Carlo simulation of a Markov process was constructed. The model incorporated surrogate outcome measures from a large randomised controlled trial (RCT) [n = 802] that compared the glycaemic and lipid control of pioglitazone and rosiglitazone monotherapy. These efficacy data were used with a recently validated and peer-reviewed UKPDS (UK Prospective Diabetes Study) algorithm to simulate the progression of these surrogate outcomes to final health outcomes, including quality of life (QOL) and mortality, and to calculate the risks of diabetic complications and death. The model perspective was of the UK NHS and included direct healthcare costs only (pounds, 2004/5 values). Patient outcomes measured in the model included life-expectancy (LE) and QALYs. The base-case analysis was run for 56-year-old male Caucasions with a haemoglobin A(1c) (HbA(1c)) of 7.57% and a body mass index of 33.14 kg/m(2). RESULTS: Patients treated with pioglitazone experienced a reduction in the total cholesterol to high-density lipoprotein-cholesterol (TC : HDL-C) ratio of 0.34, whereas the TC : HDL-C ratio increased by 0.65 in those receiving rosiglitazone (p < 0.001). The HbA(1c) profile was similar between the treatment groups (p = 0.13), as were other known risk factors for diabetes complications. The lifetime healthcare costs per patient estimated by the model were 9585 pounds for pioglitazone and 10,299 pounds for rosiglitazone. Patients treated with pioglitazone had a discounted LE of 8.83 years versus 8.79 years for those treated with rosiglitazone. Patients treated with pioglitazone also gained additional QALYs (6.8070 vs 6.7686). With improved health outcomes and lower costs, treatment with pioglitazone dominated rosiglitazone treatment. CONCLUSION: Evidence from the only large head-to-head RCT comparing rosiglitazone and pioglitazone suggests that more favourable changes in serum lipid profiles in patients treated with pioglitazone translate into improved health outcomes in terms of reduced morbidity and mortality and greater gains in QOL. In addition, this analysis indicates that treatment with pioglitazone is associated with lower costs than rosiglitazone. Therefore, in the UK, adjunctive pioglitazone may represent a cost-effective treatment choice for patients with type 2 diabetes who have insufficient glycaemic control while receiving the maximal tolerated dose of metformin monotherapy.     

The role of sulphonylureas in the management of type 2 diabetes mellitus

The sulphonylureas act by triggering insulin release from the pancreatic beta cell. A specific site on the adenosine triphosphate (ATP)-sensitive potassium channels is occupied by sulphonylureas leading to closure of the potassium channels and subsequent opening of calcium channels. This results in exocytosis of insulin. The meglitinides are not sulphonylureas but also occupy the sulphonylurea receptor unit coupled to the ATP-sensitive potassium channel.Glibenclamide (glyburide), gliclazide, glipizide and glimepiride are the primary sulphonylureas in current clinical use for type 2 diabetes mellitus. Glibenclamide has a higher frequency of hypoglycaemia than the other agents. With long-term use, there is a progressive decrease in the effectiveness of sulphonylureas. This loss of effect is the result of a reduction in insulin-producing capacity by the pancreatic beta cell and is also seen with other antihyperglycaemic agents.The major adverse effect of sulphonylureas is hypoglycaemia. There is a theoretical concern that sulphonylureas may affect cardiac potassium channels resulting in a diminished response to ischaemia.There are now many choices for initial therapy of type 2 diabetes in addition to sulphonylureas. Metformin and thiazolidinediones affect insulin sensitivity by independent mechanisms. Disaccharidase inhibitors reduce rapid carbohydrate absorption. No single agent appears capable of achieving target glucose levels in the majority of patients with type 2 diabetes. Combinations of agents are successful in lowering glycosylated haemoglobin levels more than with a single agent. Sulphonylureas are particularly beneficial when combined with agents such as metformin that decrease insulin resistance. Sulphonylureas can also be given with a basal insulin injection to provide enhanced endogenous insulin secretion after meals. Sulphonylureas will continue to be used both primarily and as part of combined therapy for most patients with type 2 diabetes.