地特胰岛素:基础胰岛素的理想选择

胰岛素是治疗糖尿病的有效药物,但胰岛素治疗在降糖的同时还会带来低血糖和体重增加等不良反应。地特胰岛素独特的分子结构和作用机制使其吸收时间减缓,同时延缓了胰岛素分子从循环血液向外周靶器官的扩散和分布,从而使其作用时间持久,并接近生理性基础胰岛素分泌,减少血糖波动。地特胰岛素对于1型糖尿病和2型糖尿病患者,均有效降低空腹血糖和HbA1c水平,且低血糖风险小,治疗引起的体重增加少。     

基础胰岛素治疗药物地特胰岛素与甘精胰岛素疗效及安全性比较

目的:比较基础胰岛素治疗药物地特胰岛素及甘精胰岛素的疗效及不良反应,为临床合理用药提供参考。方法:通过检索,对已发表的文献进行综述。结果:对于有效降低HbA1c或空腹血糖水平,地特胰岛素与甘精胰岛素作用相似;低血糖及体重增加不良反应的发生风险,地特胰岛素低于甘精胰岛素;药物经济学评估,甘精胰岛素成本低于地特胰岛素。结论:地特胰岛素与甘精胰岛素作为基础胰岛素治疗药物,疗效确切,应根据患者实际需求进行选择。     

地特胰岛素联合口服降糖药治疗2型糖尿病的有效性及安全性研究

目的 探讨地特胰岛素联合口服降糖药(OAD)治疗2型糖尿病(T2DM)的有效性和安全性.方法 符合纳入标准的56例T2DM患者随机分成两组,地特胰岛素组和中性低精蛋白锌人胰岛素(NPH)组,予睡前注射胰岛素联合口服降糖药(OAD)治疗3个月,观察3个月前后空腹血糖(FPG),餐后2h血糖(2h-PPG),糖化血红蛋白(HbA1c),血糖达标时间,达标时胰岛素用量,低血糖发生情况及体重增加情况.结果 两组FPG、2h-PPG同治疗前比较有显著下降,差异有统计学意义(P＜0.05),但治疗后组间比较差异无统计学意义(P＞0.05);HbA1c较治疗前差异性显著(P＜0.05);与对照组比较,观察组血糖达标时间短(P＜0.05),达标时胰岛素用量少(P＜0.05),低血糖发生率低(P＜0.01),体重增加小于对照组.结论 地特胰岛素联合降糖药(OAD)治疗T2DM安全有效,简便易行,血糖达标快,低血糖发生率低,胰岛素用量少.地特胰岛素在减少体重增加方面更有优势.     

地特胰岛素的体重优势:从基础到临床

体重增加是胰岛素治疗的主要障碍之一。地特胰岛素不仅能有效改善血糖控制,降低低血糖风险,还具有减少体重增加的优势。其机制可能通过抑制中枢减少能量摄人、恢复生理性肝脏/外周胰岛素梯度、减少防御性进食及减少脂肪含量等作用实现的。     

地特胰岛素有效安全降低血糖

安全、有效地控制血糖,减少糖尿病并发症的发生及相关死亡风险,可以减轻患者和社会经济负担。胰岛素治疗可以显著降低血糖,但由于低血糖和体重增加的原因,在现实生活中很多患者不愿开始胰岛素治疗。新一代基础胰岛素类似物——地特胰岛素在显著改善血糖控制的同时,具有减少低血糖风险、减少体重增加和1天1次方便使用的特点,是糖尿病患者起始胰岛素治疗的良好选择。     

地特胰岛素与甘精胰岛素治疗2型糖尿病的临床对比观察

目的 评价地特胰岛素与甘精胰岛素对口服降糖药血糖控制不佳的T2DM患者的疗效及安全性.方法 将60例口服降糖药疗效不佳的T2DM患者,随机分为地特组及甘精组,治疗3个月,观察相应指标.结果 两组FPG、2 hPG、HbA1c均较前有明显下降,与治疗前对比,P＜0.05,但在血糖下降程度、每日胰岛素用量及低血糖发生方面比较两组差异无统计学意义（P＞0.05）;两组体重均较前有所增加,但地特组的体重增加明显低于甘精组（P＜0.05）.结论 地特胰岛素与甘精胰岛素同样能有效、安全地控制血糖,在减少体重增加方面地特胰岛素更有优势.     

口服降糖药血糖控制不佳的2型糖尿病加用地特胰岛素或甘精胰岛素的疗效比较

目的评估口服降糖药血糖控制欠佳的2型糖尿病患者联合地特胰岛素或甘精胰岛素治疗的有效性和安全性。方法 90例血糖控制欠佳的2型糖尿病患者随机分为地特胰岛素组和甘精胰岛素组。在16周治疗期调整胰岛素剂量至空腹血糖≤6.0 mmol/L。记录治疗前后空腹血糖（FPG）、糖化血红蛋白（HbA1c）、低血糖事件及体重。结果治疗16周,两组FPG及HbA1c均较基线下降,两组间差异无统计学意义。两组低血糖发生率均为6.6%,但地特胰岛素组的体重增加明显低于甘精胰岛素组（P〈0.05）。结论口服降糖药血糖控制欠佳的2型糖尿病患者联合地特胰岛素或甘精胰岛素均能有效控制血糖,并且有较低的低血糖风险。相比甘精胰岛素,地特胰岛素在减少体重增加方面更有优势。     

地特胰岛素在不同糖尿病人群中的应用疗效评价

胰岛素强化治疗能够改善血糖代谢并降低微血管及大血管并发症风险已被多项大型临床研究所证实．然而,强化治疗过程中出现的低血糖及体重增加是血糖进一步达标的障碍。地特胰岛素具备药代动力学曲线较平、作用时间接近24小时、注射后患者个体变异较小等理想基础胰岛素的特点,可广泛应用于1、2型糖尿病患者,老年、儿童及妊娠糖尿病患者等不同人群．不仅能够有效降糖．还可以减少低血糖及体重增加风险．同时可以提高患者的依从性和生活满意度．值得广大临床医生结合具体实践加以推广使用,以积累更多来自中国的临床经验。     

地特胰岛素的作用机制与安全性研究进展

胰岛素是有效降糖的关键手段，其中基础胰岛素的应用是持续稳定控制血糖的重要方面。新型基础胰岛素类似物地特胰岛素以其独特的作用特点受到广泛关注，并具有一定的临床应用前景。本文将对其作用机制及安全性等方面的研究进展进行总结。     

新型基础胰岛素类似物地特胰岛素

通过文献检索综述了地特胰岛素的作用机制、药动学及临床评价。地特胰岛素是一种安全、有效的长效基础胰岛素类似物，与其他长效胰岛素相比，由于其药物分子之间的牢固结合及药物分子与血浆白蛋白的结合，从而延长了其进入循环和产生作用的时间，此作用特点使其降低血糖作用平稳而持久；与中性鱼精蛋白胰岛素相比，地特胰岛素的低血糖发生率特别是夜间低血糖发生率和增加体重的几率较低，可用于1型及2型糖尿病患者的基础血糖控制治疗。     

Insulin detemir: a review of its use in the management of type 1 and 2 diabetes mellitus

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged and consistent metabolic effect of up to 24 hours in patients with type 1 or type 2 diabetes mellitus. Insulin detemir has a more predictable, protracted and consistent effect on blood glucose than neutral protamine Hagedorn (NPH) insulin, with less intrapatient variability in glycaemic control, compared with NPH insulin or insulin glargine. Insulin detemir, administered once or twice daily, is at least as effective as NPH insulin in maintaining overall glycaemic control, with a similar or lower risk of hypoglycaemia, especially nocturnal hypoglycaemia, compared with NPH insulin in patients with type 1 or type 2 diabetes. Insulin detemir also provides the added clinical benefit of no appreciable bodyweight gain in patients with type 1 diabetes and less bodyweight gain than NPH insulin in patients with type 2 diabetes. Insulin detemir is, therefore, a promising new option for basal insulin therapy in patients with type 1 or 2 diabetes.     

Insulin detemir: from concept to clinical experience

Insulin detemir (Levemir, Novo Nordisk) is a novel, biologically engineered analogue of human insulin that has been successfully developed for clinical use in diabetes as a basal insulin. Its unique mechanism of prolongation of action, achieved through acylation to give reversible albumin binding and additional self-association, goes some way to addressing one of the fundamental limitations of previously available, subcutaneously administered basal insulins, a high level of within-person variability in time-action profile from one injection to another. The pharmacological profile of insulin detemir, characterised in a series of studies, suggested it had the potential to offer efficacy and tolerability advantages in the clinical setting. Such advantages, in comparison to NPH (neutral protamine Hagedorn) insulin, have subsequently been illustrated in trials. Despite glucose control targets that are identical to comparators, insulin detemir achieved levels of glycaemic control that, overall, were at least as good as NPH insulin in the Phase III development programme, with lower variability being a consistent finding. This was associated with consistent risk reductions in nocturnal hypoglycaemic events, which are closely linked with the basal component of insulin therapy. Another consistent finding has been a significantly reduced propensity for weight gain. An all-analogue regimen combining insulin detemir with the rapid-acting insulin aspart illustrated the potential benefits achievable when insulins that are designed to achieve defined pharmacokinetic profiles are employed clinically; blood glucose control, including hypoglycaemia, was significantly superior to a human insulin-based mealtime plus basal regimen. Insulin detemir is, therefore, a valuable addition to the range of exogenous insulins, as it should enable treatment regimens to be constructed that offer good outcomes of efficacy and tolerability.     

Defining the role of insulin detemir in Basal insulin therapy

Insulin detemir is a novel long-acting insulin analogue with a unique mechanism underlying its prolonged duration of action. Unlike neutral protamine Hagedorn (NPH) insulin (insulin suspension isophane) and insulin glargine, which precipitate after administration, insulin detemir remains soluble after it is injected. The prolonged duration of action of insulin detemir is a result of the ability to self-associate into hexamers and dihexamers, and to bind reversibly to albumin. This mechanism of protraction provides a more prolonged, consistent and predictable glycaemic effect in patients with type 1 or type 2 diabetes mellitus compared with NPH insulin. Clinical studies have demonstrated that insulin detemir administered once or twice daily is at least as effective as NPH insulin and insulin glargine in achieving glycaemic control. Most trials have also shown that insulin detemir exhibits less intrapatient variability in glycaemic control compared with NPH insulin and insulin glargine. One of the benefits of insulin detemir is its favourable effect on bodyweight. Insulin detemir has shown weight neutrality in patients with type 1 diabetes and is associated with less weight gain than NPH insulin in clinical studies. Patients with type 2 diabetes using insulin detemir gain less weight than patients using NPH insulin and insulin glargine. In addition, a reduced risk of hypoglycaemia, particularly nocturnal hypoglycaemia, has been reported with insulin detemir compared with NPH insulin in patients with type 1 and type 2 diabetes. A reduced risk of major and nocturnal hypoglycaemia compared with insulin glargine in patients with type 1 diabetes has also been observed. Together, these data indicate that insulin detemir is a valuable new option for basal insulin therapy in patients with type 1 or type 2 diabetes.     

Insulin detemir: a long-acting insulin product.

PURPOSE: The pharmacology, pharmacokinetics, efficacy and tolerability, safety, drug interactions, dosage and administration, cost, and place in therapy of insulin detemir are reviewed. SUMMARY: Insulin detemir is a long-acting, neutral, and soluble insulin analogue with a lower within-subject variability of fasting plasma glucose levels than isophane insulin human (NPH insulin) and insulin glargine. The lower within-subject variability of insulin detemir may decrease hypoglycemic events, especially nocturnal events, and may contribute to a decreased incidence of weight gain. In vivo, insulin detemir is 98-99% bound to albumin-one of the mechanisms contributing to its long duration of action. Several open-labeled, randomized, multicenter trials have been conducted comparing the safety and efficacy of insulin detemir to NPH insulin in patients with type 1 or type 2 diabetes mellitus. In most trials, patients were randomized to receive insulin on three different dosing schedules: basal insulin twice daily before breakfast and at bedtime, basal insulin at 12-hour intervals, or basal insulin before breakfast and dinner. Mealtime insulin was given as part of the basal-bolus therapy. Glycosylated hemoglobin values were similar in patients receiving insulin detemir or NPH insulin. Insulin detemir appears to be well tolerated. The most common adverse effects reported during clinical trials were hypoglycemia, headache, dizziness, and injection-site reactions. CONCLUSION: Insulin detemir given once or twice daily as part of basal-bolus insulin therapy is at least as effective as NPH insulin in maintaining overall glycemic control in adult patients with type 1 or type 2 diabetes mellitus.     

地特胰岛素联合二甲双胍治疗2型糖尿病的临床研究

目的 探讨地特胰岛素联合二甲双胍对单纯应用二甲双胍血糖控制不佳的2型糖尿病患者的疗效及安全性.方法 60例单纯应用二甲双胍治疗血糖控制不佳的2型糖尿病患者随机分为2组,分别于每日睡前应用1次地特胰岛素（Det）联合三餐口服二甲双胍（Det组,32例）、每日睡前1次中效胰岛素（NPH）联合三餐口服二甲双胍（NPH组,28例）,治疗12周.对比治疗前后空腹血糖（The fasting blood glucose,FBG）、餐后2 h血糖（2-hour blood glucose,2hBG）、糖化血红蛋白（Glycated hemoglobin,HbA1c）、体重指数（Body mass index,BMI）变化及低血糖发生情况.结果 治疗前,两组FBG、2hBG、HbA1c、BMI值比较差异无统计学意义（P〉0.05）.治疗后两组FBG、2hBG、HbA1c值均较治疗前明显下降（P〈0.05）,治疗后两组间FBG、2hBG、HbA1c比较,差异无统计学意义（P〉0.05）.Det组发生3例（3/32）低血糖,NPH组发生13例（13/28）低血糖.Det组低血糖发生情况及体重增加情况明显低于NPH组（P〈0.05）.结论 地特胰岛素与中效胰岛素联合二甲双胍,均可有效控制血糖,但地特胰岛素低血糖发生率低,在控制体重方面更有优势.     

An update on the use of insulin detemir,with a focus on type 2 diabetes (drug evaluation update)

Background: The efficacy and tolerability of insulin detemir (detemir), a long-acting basal insulin analog, is already well documented for type 1 diabetes. This article reviews new evidence, in particular on the weight-sparing effect of detemir and its use in type 2 diabetes. Methods: All clinical trials of detemir published since a 2006 drug evaluation and up to December 2007, including large real-life studies, are covered in this review. Earlier studies are cited when relevant. Results/conclusion: In type 2 diabetes, detemir used once or twice daily achieves equivalent glycemic control to other basal insulins in treat-to-target trials but tends to improve control in patients switched from other basal insulins in basal–oral regimens. The risk of hypoglycemia (nocturnal, overall, or both) is substantially and significantly reduced with detemir compared with NPH insulin. Body weight increase is consistently significantly lower with detemir than with NPH in type 1 and type 2 diabetes. The results of both glucose clamp studies and clinical trials support initiation of detemir at a once-daily dosing regimen.     

New insulin analogues and routes of delivery: pharmacodynamic and clinical considerations

Analogues of human insulin have been developed to more closely replicate the physiology of meal-related and basal insulin secretion. Three rapid-acting analogues and two basal analogues are available for clinical use. Insulin aspart and insulin lispro have nearly identical pharmacokinetic and pharmacodynamic profiles and provide better postprandial glucose control and less hypoglycaemia (primarily nocturnal and severe hypoglycaemia in type 1 diabetes mellitus) than regular insulin. Insulin glulisine is a new rapid-acting analogue and has characteristics nearly identical to those of its predecessors. Insulin glargine was the first basal analogue approved for clinical use and has shown better fasting glucose control and less risk of hypoglycaemia than conventional human neutral protamine Hagedorn (NPH) insulin. More recent studies have indicated that insulin glargine may not be truly 'peakless' at higher doses and that the adjustment of dose timing and frequency may have favourable effects on the risk of hypoglycaemia and the duration of the effect. Insulin detemir is a new basal insulin analogue with superiority to NPH insulin similar to that demonstrated by insulin glargine, though its duration of action appears to be shorter. The intraindividual variability in the response to a given dose is lower for insulin detemir than for both NPH insulin and insulin glargine. The clinical significance of this finding is not clear, though it may contribute to the lower rate of hypoglycaemia seen with insulin detemir. A number of 'alternative routes' of insulin administration have been studied, the most promising of which has been the pulmonary route. The time-action profile of inhaled insulins is generally characterized by a rapid onset of action similar to those of rapid-acting analogues and a slightly protracted duration of action similar to that of regular insulin. Inhaled insulin is similar to regular insulin with respect to efficacy and safety, though small reversible changes in pulmonary function have been noted. For technical and practical reasons, other alternative routes have generally not met with clinical success.     

Insulin analogues: place of detemir (Levemir)

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. Insulin detemir is 98-99% albumin bound in plasma. It has a more predictable glucose-lowering effect than NPH insulin or insulin glargin. There is a dose-response relationship, but at the dose of 0.4 units/kg (an average normal dose), the duration of action reaches nearly 24 h. Therefore, detemir, most often injected once per day at bedtime, seems to be the ideal basal insulin in the basal-prandial therapy for type 1 diabetic patients. The boli of insulin, in order to cover shown to reduce the risk of (severe) hypoglycaemias, particularly nocturnal (up to 50 %). Fasting hyperglycaemia is often lower, but it is not necessarily true for glycated haemoglobin. In addition, detemir has been associated with less weight gain than NPH insulin. Detemir is well tolerated and no specific safety concerns have been raised.