Insulin glulisine: a new rapid-acting insulin analogue for the treatment of diabetes

Insulin glulisine (Apidra^®, Sanofi-Aventis), a new and recently approved rapid-acting insulin analogue, mimics the pharmacokinetic and pharmacodynamic profiles of physiological human insulin, but has a rapid onset, peak effect at 1h, and a shorter duration of action (~ 4 h). Its rapid-action properties are maintained across subject types. Formal clinical evaluations show that insulin glulisine can be administered safely and effectively pre- and postmeal. When injected immediately premeal, insulin glulisine provides superior postprandial blood glucose control compared with regular human insulin (RHI) injected 30min premeal. These data highlight the flexibility in the dosing schedule with insulin glulisine. Clinical trials have demonstrated that insulin glulisine elicits a greater reduction in glycosylated haemoglobin at end point than RHI, in both type 1 and 2 diabetes mellitus. In addition, the safe administration of insulin glulisine by continuous subcutaneous insulin infusion has been demonstrated in patients with type 1 diabetes. In conclusion, insulin glulisine is an effective, safe and well-tolerated rapid-acting insulin analogue.     

Insulin glulisine: a new rapid-acting insulin analogue for the treatment of diabetes

Insulin glulisine (Apidra, Sanofi-Aventis), a new and recently approved rapid-acting insulin analogue, mimics the pharmacokinetic and pharmacodynamic profiles of physiological human insulin, but has a rapid onset, peak effect at 1h, and a shorter duration of action (approximately 4 h). Its rapid-action properties are maintained across subject types. Formal clinical evaluations show that insulin glulisine can be administered safely and effectively pre- and postmeal. When injected immediately premeal, insulin glulisine provides superior postprandial blood glucose control compared with regular human insulin (RHI) injected 30 min premeal. These data highlight the flexibility in the dosing schedule with insulin glulisine. Clinical trials have demonstrated that insulin glulisine elicits a greater reduction in glycosylated haemoglobin at end point than RHI, in both type 1 and 2 diabetes mellitus. In addition, the safe administration of insulin glulisine by continuous subcutaneous insulin infusion has been demonstrated in patients with type 1 diabetes. In conclusion, insulin glulisine is an effective, safe and well-tolerated rapid-acting insulin analogue.     

Clinical pharmacokinetics and pharmacodynamics of insulin glulisine

Insulin glulisine injection [3(B)-Lys, 29(B)-Glu-human insulin] is the newest human insulin analogue product for the control of mealtime blood sugar. As with insulin aspart and insulin lispro products, the insulin glulisine product displays faster absorption and onset of action, with a shorter duration of action than that of regular human insulin.The modifications of the amino acid sequence at positions 3 and 29 in the B chain of human insulin simultaneously provide stability to the molecular structure and render the insulin glulisine molecule less likely to self-associate, compared with human insulin, while still allowing the formation of dimers at pharmaceutical concentrations. Unlike other insulin analogue products, this allows for a viable drug product in the absence of hexamer-promoting zinc and, thus, provides immediate availability of insulin glulisine molecules at the injection site for absorption.Pharmacokinetic studies with insulin glulisine have shown an absorption profile with a peak insulin concentration approximately twice that of regular human insulin, which is reached in approximately half the time. Dose proportionality in early, maximum and total exposure is observed for insulin glulisine over the therapeutic relevant dose range up to 0.4 U/kg.The pharmacodynamic profile of insulin glulisine reflects the absorption kinetics by demonstrating a greater rate of glucose utilization, which is completed earlier and at equipotency on a molar base compared with regular human insulin. Dose-proportionality in glucose utilization has been established for insulin glulisine in patients with type 1 diabetes mellitus in the dose range of 0.075-0.15 U/kg, and a less than dose-proportional increase above 0.15 U/kg, indicating saturation of insulin action in general.The rapid absorption and action of insulin glulisine show similar low intrasubject variability compared with insulin lispro and regular human insulin when given repeatedly, and have been confirmed in healthy subjects of different body mass indices (BMIs) and ethnic groups, as well as adults and children with type 1 and type 2 diabetes. Furthermore, the early insulin exposure and action of insulin glulisine were slightly -- but consistently -- greater than those of insulin lispro in healthy volunteers across a wide range of BMIs.Meal studies in patients with type 1 diabetes show that insulin glulisine provides better postprandial blood glucose control than regular human insulin when administered immediately pre-meal, and equivalent control when given after the meal. In a study in patients with type 2 diabetes, the overall postprandial blood glucose excursions were lower with insulin glulisine than with insulin lispro. Therefore, by virtue of its primary structure, insulin glulisine demonstrates both low self-association in solution and stability for a viable insulin product in the absence of zinc, thereby maintaining immediate availability for absorption after subcutaneous injection. This confers the most rapid onset of glucose-lowering activity and adds to the flexibility in postprandial blood glucose control.     

吡格列酮或胰岛素治疗对2型糖尿病患者血尿酸的影响

目的:比较吡格列酮或胰岛素治疗对2型糖尿病患者（ type 2 diabetes mellitus T2DM）血糖及血尿酸的影响。方法：133名2型糖尿病合并高尿酸血症的患者随机分为3组,监测12周治疗前后空腹血糖、餐后2h血糖、糖化血红蛋白、血尿酸、肌酐、总胆固醇和甘油三酯。结果：吡格列酮组治疗后空腹血糖、餐后2h血糖、糖化血红蛋白、血尿酸、甘油三酯、总胆固醇等均较治疗前下降（P<0.05）。胰岛素治疗组空腹血糖、餐后2h血糖、HbA1c均较治疗前显著下降（P<0.05）。胰岛素组治疗前后空腹血糖、餐后2h血糖和HbA1c均低于吡咯列酮和常规治疗组（P<0.05）。吡格列酮组降低尿酸的作用显著高于胰岛素治疗组。常规治疗组降低血尿酸作用高于吡咯列酮组和胰岛素组。结论：胰岛素组的降糖作用最强。吡格列酮显著降低血尿酸。对于2型糖尿病合并高尿酸血症,无痛风的患者,宜选用吡格列酮。     

Defining the role of insulin lispro in the management of postprandial hyperglycaemia in patients with type 2 diabetes mellitus

The role of postprandial hyperglycaemia in contributing to the risk of both micro- and macrovascular complications in patients with diabetes mellitus is being increasingly recognized. In type 2 diabetes, there is a progressive shift in the relative contributions of postprandial and fasting hyperglycaemia to the overall glycaemic control as the disease progresses. For patients with fairly good glycaemic control (glycosylated haemoglobin [HbA(1c)] <8.5%), postprandial hyperglycaemia makes a relatively greater contribution to the overall glycaemic load than fasting hyperglycaemia, but in patients with poorer control, the relative contribution of the two states to the overall glycaemic load is reversed. This finding, coupled with epidemiological evidence that elevated postprandial glucose concentration is an independent risk factor for cardiovascular disease (CVD), and is associated with a greater CVD risk than elevated fasting glucose, points to the need to monitor and target postprandial glucose, as well as fasting glucose and HbA(1c) levels, when optimizing insulin therapy for patients with type 2 diabetes. When insulin therapy becomes necessary in patients with type 2 diabetes who can no longer be controlled with oral antihyperglycaemic therapy, use of short-acting insulin analogues with a rapid onset of action and capable of controlling postprandial glycaemic excursions when injected immediately before a meal, has advantages over regular human insulin in that they provide a more favourable time-action profile that mimics normal physiological insulin secretion. Among the available rapid-acting insulin analogues, insulin lispro has been shown to reduce postprandial glucose concentrations to a significantly greater degree than regular human insulin in patients with type 2 diabetes. Moreover, premixed combinations of insulin lispro with the longer acting analogue neutral insulin lispro protamine suspension in 25% : 75% or 50% : 50% combinations are significantly more effective in lowering postprandial blood glucose concentrations than premixed regular human insulin plus neutral protamine Hagedorn (NPH) 30% : 70%. The premixed insulin lispro combinations offer the advantage of fewer daily injections than intensive insulin therapy, and the convenience of not having to mix insulin preparations manually. Although it has yet to be conclusively established that targeting postprandial hyperglycaemia reduces CVD risk, the potential benefits of improved postprandial and interprandial hyperglycaemia favour the use of newer insulin analogues, such as insulin lispro and insulin lispro mixes, over conventional insulin therapy, whenever insulin therapy becomes necessary in patients with type 2 diabetes.     

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

Insulin aspart, a rapid-acting human insulin analogue, provides more rapid absorption than regular human insulin after subcutaneous administration. In most randomised, nonblind clinical trials in patients with type 1 diabetes mellitus, insulin aspart administered immediately before meals resulted in significantly lower mean glycosylated haemoglobin A(1c ) (HbA(1c)) levels than regular human insulin (usually administered 30 minutes before a meal). Insulin aspart also significantly improved postprandial glycaemic control compared with regular human insulin. The efficacy of insulin aspart was similar to that of insulin lispro when administered to patients with type 1 diabetes mellitus via continuous subcutaneous infusion in a randomised, nonblind trial. Preliminary data from randomised, nonblind trials suggest insulin aspart had a trend towards lower HbA(1c) levels compared with regular human insulin in patients with type 2 diabetes mellitus. Biphasic insulin aspart [30% soluble (rapid-acting) and 70% protamine-bound insulin aspart (BIAsp30)] generally provided significantly better postprandial glucose control than a similar mixture of biphasic regular human insulin (BHI30) in a randomised, nonblind trial in patients with type 1 or 2 diabetes mellitus. However, the long-term efficacy of BIAsp30 was similar to that of BHI30 after 2 years in a randomised, nonblind trial in patients with type 2 diabetes mellitus. Patients with type 1 or 2 diabetes mellitus reported greater treatment satisfaction with insulin aspart or BIAsp30 than with regular human insulin or BHI30. The overall incidence of hypoglycaemia with insulin aspart was lower than, or similar to, that of regular human insulin. Moreover, insulin aspart tended to be associated with a lower occurrence of nocturnal hypoglycaemia and severe hypoglycaemic events than regular human insulin. CONCLUSION: The standard preparation of insulin aspart has the potential to better mimic the physiological response to meals than regular human insulin. Insulin aspart when combined with a suitable basal insulin improved overall glycaemic control and led to a similar or lower number of hypoglycaemic episodes compared with a similar regular human insulin regimen. Insulin aspart was generally as effective and well tolerated as insulin lispro when administered by continuous subcutaneous infusion in a single comparative trial. The efficacy of biphasic insulin aspart has been documented in a small number of trials. Both insulin aspart and biphasic insulin aspart provide for flexible and convenient administration. Insulin aspart is now well established as an effective and convenient means of providing glycaemic control which offers clinical and practical advantages over regular human insulin.     

Insulin glulisine--a comprehensive preclinical evaluation

Receptor binding and signaling and the mitogenic potential of insulin glulisine (glulisine), regular human insulin (RHI), and Asp(B10) were compared in vivo and in vitro. Insulin and insulin-like growth factor 1 (IGF-1) receptor binding was studied with human insulin receptors (293HEK cells) and the human osteosarcoma-derived cell line B10. Insulin receptor-mediated signaling was assessed in rat-1 fibroblasts overexpressing insulin receptors. Activation of insulin receptor substrates 1 and 2 (IRS-1/ IRS-2) was studied in rat and human myoblasts and rat cardiomyocytes. DNA synthesis induction was assessed by [3H] thymidine incorporation in the human epithelial breast cell line MCF10. Interaction with the IGF-1 receptor, DNA synthesis, and intracellular signal transduction were assessed in cardiac K6 myoblasts. Immunohistochemical examination of Sprague-Dawley rat tissue treated with glulisine for 6 months (n = 40), and glulisine and RHI for 12 months (n = 60), was performed. Steady-state insulin receptor binding affinity was slightly lower for glulisine versus RHI (approximately 0.70). IGF-1 receptor binding affinity was lower (four- to fivefold) for glulisine, but significantly higher (four-fold) for Asp(B10) versus RHI. Glulisine, Asp(B10), and RHI showed similar insulin receptor-association kinetics; however, Asp(B10) revealed increased insulin receptor affinity. Glulisine and RHI showed similar insulin receptor-mediated phosphorylation and IRS-2 activation. Activation of IRS-1 was 6- to 10-fold lower with glulisine; glulisine was less potent and Asp(B10) slightly more potent in stimulating DNA synthesis versus RHI. Stimulation of DNA synthesis was comparable for glulisine and RHI in K6 myoblasts. At 12 months, there was no significant difference between glulisine and RHI in proliferative activity. This preclinical evaluation suggests that structural changes in glulisine versus RHI are not associated with any safety issues.     

Insulin glulisine

In patients with diabetes, the benefit of conventional insulin therapy can be limited due to difficulty in achieving tight glycemic control, which is critical to reducing the risk of long-term diabetes-related complications. The recent development of recombinant analogs of regular human insulin is changing the clinical management of diabetes. One of the newest members of this class of hypoglycemic agents is insulin glulisine, a rapid-acting insulin analog with a pharmacokinetic profile that more closely mimics the natural pattern of insulin secretion than regular human insulin. Subcutaneous administration of insulin glulisine has a faster subcutaneous absorption, a more rapid onset of activity, and a shorter duration of action than regular human insulin. These properties of insulin glulisine allow it to be administered shortly before or soon after meals by subcutaneous injection or by continuous subcutaneous pump infusion. Insulin glulisine effectively controls postprandial glucose excursions in both type 1 and type 2 diabetic patients without increasing the risk of hypoglycemia. One unit of insulin glulisine has the same glucose-lowering effect as one unit of regular human insulin. Insulin glulisine has a favorable safety profile, which is not significantly different from that of regular human insulin. This review summarizes the current data on the clinical efficacy and safety of insulin glulisine in type 1 and type 2 diabetic patients.     

抗糖尿病新药格鲁辛胰岛素

综述了格鲁辛胰岛素的作用机制、药动学及临床评价。格鲁辛胰岛素是一种最新通过美国FDA批准的快速胰岛素类似物，用于控制1型和2型糖尿病。与常规胰岛素相比，它起效快，维持作用时间短，与长效胰岛素合用或用于胰岛素泵，可维持正常的血糖控制。     

优泌乐25联合二甲双胍治疗预混人胰岛素70/30血糖控制欠佳的2型糖尿病患者的疗效

目的研究2次/d预混人胰岛素70/30治疗血糖控制欠佳的2型糖尿病患者转用优泌乐25联合二甲双胍治疗的有效性和安全性。方法 2次/d注射预混人胰岛素70/30(联合或不联合口服降糖药)血糖控制欠佳的2型糖尿病患者54例,换用优泌乐25联合二甲双胍治疗。在治疗开始及12周分别记录空腹血糖、餐后2 h血糖、HbA1c(糖化血红蛋白)、体重指数及胰岛素剂量。结果治疗12周后,空腹血糖、餐后2 h血糖、HbA1c、体重指数及胰岛素剂量均较基线水平显著下降。出现低血糖12例。结论应用预混人胰岛素70/30治疗血糖控制欠佳的2型糖尿病患者,转用优泌乐25联合二甲双胍治疗后,其血糖可得到安全、有效的控制。     

精蛋白锌重组赖脯胰岛素混和注射液对初诊糖尿病血糖及胰岛功能的影响

目的探讨精蛋白锌重组赖脯胰岛素混和注射液（优泌乐25）强化治疗对初诊2型糖尿病患者血糖及胰岛功能的影响。方法对60例初诊2型糖尿病患者进行2个月的优泌乐25治疗,观察治疗前后空腹血糖（FPG）及餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）、胰岛素抵抗指数、胰岛素分泌指数、胰岛素敏感指数、空腹胰岛素（FINS）与FPG比值。结果优泌乐25治疗后,FPG、2hPG、HbA1c、胰岛素抵抗指数均较治疗前明显下降（P〈0．01）;空腹C肽的分泌、胰岛素、FINS与FPG比值、胰岛素分泌指数、胰岛素敏感指数均较治疗前明显升高（P〈0．01）。结论优泌乐25强化治疗能显著改善初诊2型糖尿病患者的血糖及胰岛功能。     

Clinical pharmacokinetics and pharmacodynamics of insulin aspart

Insulin aspart is a novel rapid-acting insulin analogue with improved subcutaneous absorption properties when compared with soluble human insulin. Pharmacokinetic studies show an absorption profile with a time to reach peak concentration (t(max)) about half that of human insulin, a peak plasma drug concentration (Cmax) approximately twice as high and shorter residence time. The potency and bioavailability of insulin aspart are similar to those of human insulin. The pharmacokinetics of insulin aspart have been studied in healthy Caucasian and Asian-Japanese volunteers, in patients with type 1 and 2 diabetes mellitus, and in children with diabetes, with both pre- and postprandial administration and during continuous subcutaneous insulin infusion (CSII). The pharmacokinetic profile was similar to that of another rapid-acting insulin analogue, insulin lispro, on the basis of published information for that agent. Pharmacodynamic studies show a smaller excursion of postprandial glucose with insulin aspart injected subcutaneously just before the meal compared with soluble human insulin injected 30 minutes before the meal in patients with type 1 diabetes mellitus, and an equivalent control in patients with type 2 diabetes displaying residual insulin production. In a treatment study, glucose excursions evaluated from 24-hour glucose profiles showed less variability with insulin aspart compared with human insulin. Adverse events, including hypoglycaemia-induced ventricular repolarisation and hypoglycaemic threshold and awareness, did not differ between insulin aspart and human insulin. The available data suggest that subcutaneous injections of insulin aspart just before meals better mimic the endogenous insulin profile in blood compared with human insulin, resulting in improved glucose control in a meal-related insulin regimen. This review summarises the clinical pharmacokinetics and pharmacodynamics of insulin aspart in relation to human insulin and insulin lispro.     

Insulin aspart: a review of its use in the management of type 1 or 2 diabetes mellitus

Insulin aspart (NovoRapid, NovoLog) is a short-acting insulin analogue, which has a faster onset and shorter duration of action than regular human insulin. Insulin aspart administered immediately before meals provided significantly greater improvements in glycosylated haemoglobin and better postprandial glycaemic control than regular human insulin administered 30 minutes before meals, when used in a basal-bolus regimen with neutral protamine Hagedorn (NPH) insulin, in randomised, nonblind studies in patients with type 1 diabetes mellitus. In patients with type 2 diabetes, insulin aspart provided similar glycaemic control to regular human insulin, administered in a basal-bolus regimen with NPH insulin. Small studies suggest that the use of insulin aspart in combination with oral hypoglycaemic agents may be beneficial. Insulin aspart, administered by continuous subcutaneous insulin infusion (CSII) provided better glycaemic control than insulin aspart multiple daily injection regimens in patients with type 1 (but not type 2) diabetes, and had similar efficacy to CSII with insulin lispro or regular human insulin in type 1 diabetes. Limited studies show insulin aspart to be effective in children, adolescents and young adults with type 1 diabetes. Insulin aspart had a tolerability profile similar to that of regular human insulin in clinical trials. The incidence of major or nocturnal hypoglycaemic events reported in patients receiving insulin aspart was lower than that of regular human insulin in several studies.In conclusion, insulin aspart, administered immediately before meals in a basal-bolus regimen with NPH insulin, provided better long-term glycaemic control than regular human insulin administered 30 minutes before meals in patients with type 1 diabetes, and was as effective as regular human insulin in patients with type 2 diabetes. A significantly lower risk of hypoglycaemia was seen in several trials. Insulin aspart CSII provided better glycaemic control than insulin aspart multiple daily subcutaneous injection (MDI) in patients with type 1 (but not type 2) diabetes and had similar efficacy to CSII with insulin lispro or regular human insulin in type 1 diabetes. Insulin aspart is an effective and well tolerated alternative to regular human insulin and insulin lispro for the maintenance of glycaemic control in patients with type 1 or 2 diabetes.     

门冬胰岛素在青少年1型糖尿病胰岛素泵中的应用

目的:评价新型速效胰岛素类似物门冬胰 岛素注射液在中国青少年1型糖尿病胰岛素泵治疗 中的有效性和安全性并与常规人胰岛素泵治疗比 较。方法:10例正在使用胰岛素泵的青少年1型糖 尿病病人,年龄(13±s3)a,进行4wk的纳入期(继 续常规人胰岛素治疗)和8wk的治疗期(改用门冬 胰岛素治疗),共12wk的研究,观察治疗前后餐后 2h血糖(PBG)、空腹血糖(FBG)、糖化血红蛋白 (HbA1c)和不良反应。结果:治疗8wk后,FBG, PBG和HbA1c分别由(9±3)mmol·L-1,(11.6± 2.7)mmol·L-1和(9.1±2.0)%下降至(6± 3)mmol·L-1,(7±3)mmol·L-1和(7.6± 1.2)%。PBG和HbA1c与治疗前比较差异有非常 显著和显著意(P<0.01,P<0.05)。治疗过程中 低血糖事件无明显增加。结论:门冬胰岛素能有效 降低青少年1型糖尿病病人PBG和HbA1c,无明显 不良反应,是目前胰岛素泵治疗中满意的胰岛素类 型。     

吡格列酮联合胰岛素对2型糖尿病患者脂联素水平的影响

目的观察吡格列酮联合胰岛素治疗2型糖尿病对患者血浆脂联素水平的影响。方法60例2型糖尿病患者随机分为2组,分别给予胰岛素及吡格列酮联合胰岛素治疗,疗程共12周。分别检测和记录2组患者治疗前后空腹血糖(FBG)、糖化血红蛋白(HbA1c)、脂联素以及胰岛素用量,观察吡格列酮对2型糖尿病患者血浆脂联素的影响。结果2组患者治疗后血糖和HbA1c均控制良好,其中观察组胰岛素日需求量明显低于对照组(P<0.05);观察组血浆脂联素水平较对照组明显升高(P<0.05)。结论吡格列酮联合胰岛素治疗2型糖尿病不仅可良好地控制血糖HbA1c,同时增加患者血浆脂联素水平,提高患者对胰岛素的敏感性,减少胰岛素用量。     

赖脯胰岛素25不同给药次数治疗2型糖尿病的有效性及安全性

目的评价对于血糖初诊高、降糖口服药及其他类胰岛素控制血糖效果较差的2型糖尿病（DM）患者,应用赖脯胰岛素治疗的临床疗效、安全性观察。方法选取2008年1月-2010年12月本院采用赖脯胰岛素25治疗的120例2型DM患者,66例2次／d皮下注射（2次组）;54例3次／d皮下注射（3次组）。随访3个月,对比两组患者临床资料差异情况。结果两组经14d治疗后血糖值均较治疗前下降明显（P〈0．001）,两组血糖下降差异无统计学意义（P〉0．05）。住院期间2次组发生低血糖事件17例,3次组发生1l例;2次组胰岛素用量为（0．44±0．14）U／kg,3次组胰岛素用量为（0．62±0．16）U／kg,组间差异有统计学意义（P〈0．05）。结论2次／d或3次／d赖脯胰岛素25皮下注射,对2型DM患者,均可控制HbAlc。及血糖,3次／d效果较满意且无增加低血糖风险的发生率。     

三联疗法治疗磺酰脲类药物继发失效2型糖尿病的临床观察

目的:观察甘精胰岛素、瑞格列奈、罗格列酮联合治疗磺酰脲类药物继发失效(SFS)的2型糖尿病(T2DM)患者的血糖(BG)控制和胰岛B细胞功能恢复情况。方法:选择26例三联疗法治疗的SFS患者,采用自身前、后对照观察空腹血糖(FPG)、餐后2 h血糖(2hPG)、空腹基础C肽值(FC-P)、餐后2hC肽值(2hC-P)、糖化血红蛋白(HbA1c)等变化。结果:与治疗前比较,甘精胰岛素、瑞格列奈、罗格列酮联合治疗SFS的T2DM,BG控制理想,胰岛B细胞功能改善均有统计学意义(P<0.05)。结论:甘精胰岛素、瑞格列奈、罗格列酮三联疗法能有效控制SFS的T2DM患者BG,并能改善胰岛B细胞功能。     

Safety of insulin analogues as compared with human insulin in pregnancy

ABSTRACT

Introduction: Diabetes during pregnancy may lead to maternal, fetal and neonatal complications. In order to limit unwarranted outcomes, strict glycemic control is essential. In the past, human insulin was the only insulin formulation administered in pregnancy. However, insulin analogues have also been used for this indication in recent years.

Areas covered: This article reviews the published data regarding the safety of insulin analogue use during pregnancy. We present the qualities, advantages and pitfalls of insulin analogue use in pregnancy compared with human insulin. Insulins lispro, aspart and detemir are safe in pregnant women with type 1 diabetes. Correspondingly, they were reclassified for the treatment of pregnant women with diabetes from category C to category B. For insulin glargine use in pregnancy, most studies are small and retrospective. Yet, no major safety concerns were reported. Insulin glulisine and degludec have not been studied in pregnancy.

Expert opinion: Insulin analogues are viable therapeutic options for diabetes in pregnancy, specifically lispro, aspart and detemir. Though data in limited, their safety and efficacy are comparable with human insulin. Remarkably, the analogues are superior to human insulin regarding hypoglycaemia risk. More data, specifically for their use in pregnancies complicated by gestational diabetes or type 2 diabetes, is needed.     

Insulin therapy in type 2 diabetes

OBJECTIVE: To review the increasingly common use of insulin therapy in patients with type 2 diabetes and the practical aspects of initiating insulin therapy in these patients. DATA SOURCES: Recent scientific and clinical literature identified through MEDLINE searches for the years 1995-2001 using the terms oral agents, type 2 diabetes, insulin therapy, glycemic control and diabetic complications, glucose toxicity, insulin lispro, insulin aspart, and insulin glargine. STUDY SECTION: Reports of key large (1,000 patients or more) and significant smaller, randomized, controlled clinical trials were reviewed. For studies comparing insulin analogs, the authors reviewed a sampling of the identified trials for their characteristics and clinical importance. DATA SYNTHESIS: Tight blood glucose control can help reduce the risk of diabetes complications. Evidence suggests that early insulin therapy can help correct the underlying pathogenetic abnormalities in type 2 diabetes and improve long-term glycemic control. For these reasons, some diabetes experts advocate the initiation of insulin therapy earlier in the course of type 2 diabetes than has been common in the past. Insulin regimens should be designed to mimic the body's natural physiologic secretion of insulin, including the basal amounts released continuously by the pancreas and the insulin surges produced in response to glucose loads. Using new insulin analogs is a useful approach to achieving this ideal. Insulin glargine provides a nearly constant, peakless release of insulin when injected subcutaneously once daily. Two new rapid-acting insulin analogs, insulin lispro (Humalog--Lilly) and insulin aspart (NovoLog--Novo Nordisk), enhance patients' flexibility in terms of meals by permitting injection immediately before meals, rather than 30 minutes before meals, as with regular insulin. CONCLUSION: Patients should be reassured that early initiation of insulin therapy is a positive event that should improve their long-term health and does not represent a decline in the course of their disease.     

Insulin lispro: a review of its use in the management of diabetes mellitus

Insulin lispro, alone (Humalog) or as premixture (Humalog Mix25 or Humalog Mix50) is indicated for the treatment of hyperglycaemia in diabetes mellitus in many countries worldwide. It is a recombinant human insulin analogue and, except for the transposition of two amino acids, is identical to endogenous human insulin. Insulin lispro has a faster onset of action and shorter duration of activity than regular human insulin, and the time-action profile of insulin lispro mimics that of the physiological response of endogenous human insulin to food intake. In diabetic patients, from young children to the elderly, it has demonstrated postprandial blood glucose control similar to or better than that achieved with regular human insulin, without an increased risk of hypoglycaemia. In some trials, the risk of hypoglycaemia, including nocturnal episodes, was less in insulin lispro recipients than in regular human insulin recipients. Insulin lispro alone, or as a premixture with the longer-acting insulin neutral protamine lispro, can be administered immediately before or after meals. This convenient and flexible injection schedule may enable patients, including those with a non-routine lifestyle or unpredictable eating or exercising habits, to achieve the tight glycaemic control required to minimise long-term complications of diabetes and contributes to patient satisfaction with treatment.