Insulin glargine: a new long-acting insulin product.

The pharmacodynamics, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of insulin glargine are reviewed. Current treatment regimens for patients with type 1 diabetes mellitus and some with type 2 are designed to provide a basal insulin level with intermittent preprandial insulin coverage. Insulin glargine precipitates after subcutaneous injection, slowing absorption. Insulin glargine is used as a basal insulin and exhibits a flat pharmacokinetic profile, with a duration of action of at least 24 hours. Hypoglycemia is the most commonly reported adverse effect, especially within the first four weeks after a switch to insulin glargine. Insulin glargine should not be mixed with any other insulin product and should be administered with a syringe that has not been used for other insulin products or other medications. Insulin glargine is administered once daily at bedtime. Patients previously receiving twice-daily isophane insulin (NPH) should receive an insulin glargine dosage 20% less than the total daily dose of NPH insulin. Clinical trials did not consistently show improvements in hemoglobin A1c levels when patients with type 1 diabetes mellitus were switched from NPH insulin once or twice daily to insulin glargine. Insulin glargine should be considered for patients who continue to have elevated morning blood glucose levels and problems with nocturnal hypoglycemia despite receiving NPH insulin at bedtime. In patients with type 2 diabetes mellitus, insulin glargine significantly improved glycemic control compared with once-daily NPH insulin, but not when it was compared with combined treatment with once- or twice-daily NPH insulin. Clinical trials assessing progression of retinopathy and nephropathy and comparing insulin glargine therapy with continuous subcutaneous insulin infusion therapy are needed to more clearly determine insulin glargine's role. Insulin glargine is a new long-acting formulation that can provide prolonged basal glucose control in patients with diabetes mellitus.     

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 glargine: a review of its therapeutic use as a long-acting agent for the management of type 1 and 2 diabetes mellitus

Insulin glargine is a recombinant human insulin analogue produced by DNA technology using a nonpathogenic strain of Escherichia coli. Two modifications of human insulin result in a stable molecule which is soluble in slightly acidic conditions (pH 4.0) and precipitates in the neutral pH of subcutaneous tissue. Because of these properties, absorption of insulin glargine is delayed and the analogue provides a fairly constant, basal insulin supply without peaks in plasma insulin levels for approximately 24 hours, similar to that achieved by a continuous subcutaneous insulin infusion. Insulin glargine is indicated as a once daily subcutaneous injection to provide basal glycaemic control in adults and children aged >6 years with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Fasting plasma glucose and fasting blood glucose levels generally improved to a greater extent in patients with type 1 diabetes mellitus receiving insulin glargine than patients who administered Neutral Protamine Hagedorn (NPH) insulin. In patients with type 1 or 2 disease, glycosylated haemoglobin levels were slightly reduced and to a similar extent with insulin glargine and NPH insulin. Most clinical trials in patients with type 1 or 2 diabetes mellitus demonstrated a lower incidence of hypoglycaemia, especially nocturnal hypoglycaemia, compared with NPH insulin. One of the most common adverse events with insulin glargine treatment was injection site pain which, in some studies, occurred more frequently than in patients receiving NPH insulin. In all cases the symptoms were mild and treatment discontinuation was not required. Otherwise, the drug is well tolerated and does not appear to be immunogenic. CONCLUSIONS: Insulin glargine once a day provides basal control of glycaemia for approximately 24 hours without inducing peaks in plasma insulin levels in patients with type 1 or 2 diabetes mellitus. In long term, well designed trials insulin glargine once daily improved glycaemic control at least as effectively as NPH insulin given once or twice daily. The drug was well tolerated and in most studies the incidence of nocturnal hypoglycaemia was significantly less in patients treated with insulin glargine compared with patients receiving NPH insulin. Therefore, insulin glargine is likely to be a useful addition to the armamentarium of insulin therapy by establishing basal glycaemic control with once daily administration and a reduced risk of nocturnal hypoglycaemia.     

Insulin glargine: an updated review of its use in the management of diabetes mellitus

Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine for up to 39 months in adults and children with type 1 and adults with type 2 diabetes. In conclusion, insulin glargine is an effective and well tolerated basal insulin therapy when given as a single daily subcutaneous injection to patients with diabetes, with benefits in terms of glycaemic control and reduced frequency of hypoglycaemia over regimens based on conventional basal insulins. Accumulating data and official recommendations show the suitability of insulin glargine for first-line use in selected patients with type 2 diabetes who require insulin treatment, as well as in patients with type 1 disease, and confirm its use in children and adolescents.     

Insulin glargine: long-acting basal insulin analog for improved metabolic control

The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes in a physiologically sound manner, mimicking normal secretion patterns to adequately regulate glucose metabolism. The currently available human insulins for basal therapy--neutral protamine Hagedorn (NPH), Lente and Ultralente--and analogs such as insulin glargine, differ in pharmacokinetic properties. Clinical trial data indicate that insulin glargine may satisfy basal insulin requirements, with an improved safety profile relative to other available insulins used for basal supplementation. This review describes the unique pharmacokinetic properties and clinical efficacy of insulin glargine.     

Insulin detemir: new drug. A second long-acting insulin analogue: many uncertainties, few advantages

(1) The standard treatment for type 1 diabetes is intensive insulin therapy, consisting of at least 3 daily injections of different insulins, one of which is a long-acting insulin. (2) Insulin detemir is the second long-acting human insulin analogue to be marketed in Europe (after insulin glargine) for the treatment of diabetes in adults and children over 6 years of age. Its action lasts about 12 hours. (3) Insulin detemir was evaluated in around 10 comparative trials, all unblinded, examining the effect of insulin detemir in terms of global glycaemic control (HbA1c level). None of these trials examined whether insulin detemir prevented complications of diabetes. (4) About 10 trials, involving more than 3000 patients, showed that insulin detemir, insulin isophane and insulin glargine have similar efficacy in treating both type 1 and type 2 diabetes. (5) The short-term adverse effect profile of insulin detemir is similar to that of isophane insulin. There is slightly less weight gain with insulin detemir, but injection site reactions occur more frequently. The long-term adverse effects of insulin detemir are not known. (6) Insulin detemir is a clear solution, leading to a risk of confusion with ordinary human insulin or a fast-acting insulin analogue. (7) In practice, isophane insulin remains the first choice long-acting insulin for patients with type 1 or type 2 diabetes.     

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 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.     

Insulin glargine in the management of diabetes mellitus: an evidence-based assessment of its clinical efficacy and economic value

INTRODUCTION: Diabetes is a chronic disease associated with high morbidity and mortality, which represents a major public health concern. Interventions that can enhance patient care and reduce clinic visits will not only relieve some of this burden, they will also improve patient QOL and wellbeing. AIMS: This review assesses the evidence for the use of insulin glargine in type 1 and type 2 diabetes mellitus. EVIDENCE REVIEW: Once-daily insulin glargine has a prolonged, peakless activity profile, making it a candidate as a long-acting (basal) insulin. In combination with bolus insulin to cover prandial glucose surges, it facilitates a more physiologic approach to patient management. Evidence from large, randomized, controlled clinical trials in patients with type 1 diabetes has confirmed its effectiveness and tolerability relative to neutral protamine hagedorn (NPH) insulin, with a tendency toward causing less hypoglycemia. In patients with type 2 diabetes requiring insulin therapy, once-daily insulin glargine has proven to be clinically superior to NPH insulin in terms of providing at least as effective glycemic control, but with significantly fewer episodes of nocturnal hypoglycemia. A variety of economic analyses have confirmed the cost effectiveness of insulin glargine in type 1 and type 2 diabetes and in particular it was shown to be significantly superior to NPH insulin. CLINICAL VALUE: Insulin glargine has established itself as a first-line choice in patients with type 1 diabetes, including children (>6 years) and adolescents, and is a recommended treatment option. In patients with type 2 diabetes it is clearly associated with less hypoglycemia than NPH insulin, and this may help overcome one of the major barriers to starting insulin therapy in this class of patient. Thus, insulin glargine is a valuable addition to the therapeutic armamentarium available to physicians and it has the potential to significantly improve the quality of life of patients with diabetes.     

Insulin glargine (Aventis Pharma)

Insulin glargine is a biosynthetic human insulin analog which has been developed by Aventis Pharma (formerly Hoechst Marion Roussel, HMR), for the treatment of types I and II diabetes. In April 1999, HMR filed insulin glargine for approval in both Europe and the US [322507]. In April 2000, the FDA approved insulin glargine (as Lantus) for the treatment of adult patients with type II diabetes mellitus, who require basal insulin for the control of hyperglycemia, and for adult and pediatric patients with type I diabetes mellitus [363836]. Aventis expects to launch this product during 2000 [361988]. In June 2000, the EMEA approved insulin glargine for the treatment of both type I and II diabetes [370984]. In April 1999, the FDA recommended that HMR should initially submit 6-month efficacy and safety data, instead of the usual 12- month data, to hasten the FDA approval procedure. The rest of the phase III data would be added to the filing at a later date [279466]. Insulin glargine is in phase III trials in Japan as a substitute for basal insulin in the treatment of Type I diabetes [216445]. Two formulations of insulin glargine with zinc have also been tested in phase I trials. HOE-71/GT15 and GT80 contain 15 and 80 mu g/ml of zinc. These formulations appear to have longer duration of action with a reduced peak insulin effect [177507]. This insulin analog has a lower receptor binding affinity compared with human insulin, but shows equal potency in vivo [320724]. Insulin glargine was designated as a medium priority project by HMR, which means the project had been set tight deadlines which if not achieved, would have resulted in discontinuation [221118]. In April 2000, Novo Nordisk filed a complaint in Germany against Aventis claiming that the production and sale of insulin glargine infringes two German patents held by Novo Nordisk [364362]. In July 2000, Credit Lyonnais Securities Europe predicted that insulin glargine was likely to enjoy a strong competitive position for several years in Europe and the US, following launch in these territories during 2000, while it was predicted that a registration dossier would be submitted in Japn in 2002. Sales were predicted to reach Euro 600 million by 2005. In April 1999, ABN Amro predicted annual sales of DM 75 million in 2000, rising to DM 200 million in 2002 [328676].     

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 glargine: long-acting basal insulin analog for improved metabolic control

SUMMARY

The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes in a physiologically sound manner, mimicking normal secretion patterns to adequately regulate glucose metabolism. The currently available human insulins for basal therapy - neutral protamine Hagedorn (NPH),Lente^* and Ultralente^? – and analogs such as insulin glargine, differ in pharmacokinetic properties. Clinical trial data indicate that insulin glargine may satisfy basal insulin requirements, with an improved safety profile relative to other available insulins used for basal supplementation. This review describes the eunique pharmacokinetic properties and clinical efficacy of insulin glargine.     

于精胰岛素联合瑞格列奈治疗2型糖尿病的临床观察

目的：观察甘精胰岛素联合瑞格列奈治疗2型糖尿病的临床疗效。方法：将48例2型糖尿病患者随机分成甘精胰岛素组和对照组各24例,比较两组的空腹血糖、餐后2h血糖、胰岛素剂量、低血糖发生次数。结果：两组患者的空腹血糖及餐后2h血糖较治疗前显著降低（P〈0.05）;甘精胰岛素组达标高于对照组,差异有统计学意义（P〈0.05）;甘精胰岛素组胰岛素剂量较对照组少,差异有统计学意义（P〈0.05）;低血糖发生率低（P〈0.05）。结论：甘精胰岛素联合瑞格列奈能有效控制2型糖尿病,不易出现低血糖,值得临床广泛应用。     

Cancer risk in diabetic patients treated with insulin glargine?

Insulin glargine was the first long-acting human insulin analogue to be authorised in the European Union, in the early 2000s, for the treatment of diabetes mellitus. It has about a 6-fold increase in affinity for the insulinlike growth factor 1 (EGF-1) receptor compared with natural human insulin, which may stimulate tumour development. Four European epidemiological studies published in 2009 examined the risk of cancer in diabetic patients treated with insulin glargine. One of these studies, conducted in Germany, showed a statistically significant dose-dependent increase in the risk of cancer. Two other studies, one in Scotland and the other in Sweden, showed an increase in the risk of breast cancer. The fourth study, conducted in the UK, showed a lower risk of cancer in patients on metformin. This evidence is inconclusive, notably because these studies did not take confounding factors into account. Nevertheless, the results tend to be similar and consistent with certain pharmacological mechanisms. In practice, pending more solid evidence, these epidemiological results should be taken into account when weighing the risk-benefit balance of insulin therapy for diabetic patients, on a case by case basis, depending on the type of diabetes, patient history, life expectancy, and the possible practical advantages of insulin glargine.     

甘精胰岛素联合格列美脲和阿卡波糖治疗磺脲类药物治疗失效的2型糖尿病的疗效观察

目的探讨甘精胰岛素注射液联合格列美脲片和阿卡波糖片治疗磺脲类药物治疗失效的2型糖尿病的临床疗效。方法选取2014年10月—2016年6月中山大学附属第三医院粤东医院内分泌科收治的磺脲类药物治疗失效的2型糖尿病患者136例,按照治疗方案的不同分为甘精胰岛素联合格列美脲组(44例)、甘精胰岛素联合阿卡波糖组(43例)、甘精胰岛素联合格列美脲和阿卡波糖组(49例)。甘精胰岛素联合格列美脲组每日晚餐后皮下注射甘精胰岛素注射液,起始剂量10 U/d;晚餐后30 min口服格列美脲片2 mg。甘精胰岛素联合阿卡波糖组每日晚餐后皮下注射甘精胰岛素注射液,起始剂量10 U/d;口服阿卡波糖片50 mg,3次/d;甘精胰岛素联合格列美脲和阿卡波糖组每日晚餐后皮下注射甘精胰岛素,起始剂量10 U/d;晚餐后30 min口服格列美脲片2 mg;口服阿卡波糖片50 mg,3次/d。治疗3个月后比较各观察指标。结果治疗后,3组空腹血糖(FBG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)水平均降低(P0.05),且甘精胰岛素联合格列美脲和阿卡波糖组血糖指标改善优于甘精胰岛素联合格列美脲组、甘精胰岛素联合阿卡波糖组(P0.05)。治疗后,3组稳态模型评估胰岛素抵抗指数(HOMA-IR)降低,胰岛β细胞功能指数(HOMA-β)、餐后2 h胰岛素、餐后2 h C-肽均升高(P0.05),且甘精胰岛素联合格列美脲和阿卡波糖组胰岛功能改善优于甘精胰岛素联合格列美脲组、甘精胰岛素联合阿卡波糖组(P0.05)。甘精胰岛素联合格列美脲和阿卡波糖组血糖达标时间短于甘精胰岛素联合格列美脲组、甘精胰岛素联合阿卡波糖组(P0.05),胰岛素日用量低于甘精胰岛素联合格列美脲组、甘精胰岛素联合阿卡波糖组(P0.05),低血糖发生率低于甘精胰岛素联合格列美脲组(P0.05),而与甘精胰岛素联合阿卡波糖组差异无统计学意义。结论甘精胰岛素注射液联合格列美脲片和阿卡波糖片治疗磺脲类药物治疗失效的2型糖尿病可有效控制血糖水平,缩短血糖达标时间,且不增加低血糖发生率,具有一定的临床推广应用价值。     

甘精胰岛素的临床评价

甘精胰岛素是由DNA重组技术制备的一种重组人胰岛素类似物,为长效降糖药。甘精胰岛素的作用较为平稳,血浓度无峰值,作用时间持久(可达24h)。因此,每天1次剂量如同生理基础胰岛素。甘精胰岛素的不良反应主要为低血糖,但其夜间低血糖的发生率明显低于其他某些胰岛素制剂。     

甘精胰岛素联合瑞格列奈治疗初发2型糖尿病的临床观察

目的分析了甘精胰岛素与瑞格列奈联合治疗初发2型糖尿病的疗效。方法徐州市中心医院于2009年至2011年共收治2型糖尿病患者40例,所有患者初诊均为2型糖尿病,40例患者每天皮下给予甘精胰岛素1次,主要控制患者的空腹状态下的血糖浓度,并在患者三餐之前口服瑞格列奈对用餐后的血糖水平进行控制。治疗4个月之后对患者空腹血糖水平、餐后2h的血糖水平、糖化血红蛋白水平以及空腹状态下胰岛素的浓度、C肽和进餐后2h的胰岛素、C肽进行分析。结果与治疗前比较,治疗后患者空腹血糖水平和餐后2h的血糖水平显著性下降,具有统计学意义(P<0.05);治疗前后糖化血红蛋白的水平治疗前相比较,患者治疗之后胰岛素以及C肽浓度均有显著性的改善(P<0.05)。结论甘精胰岛素与瑞格列奈联合治疗2型糖尿病疗效显著可很好的控制患者血糖浓度,对患者β细胞功能恢复意义重大,值得临床推广使用。     

地特胰岛素与甘精胰岛素治疗早期2型糖尿病疗效比较

目的：比较地特胰岛素与甘精胰岛素治疗早期2型糖尿病的疗效。方法：50例早期初发2型糖尿病患者（7．0≤空腹血糖≤13．9mmol·L^-1）随机分为治疗组（给予地特胰岛素）和对照组（给予甘精胰岛素）,均按初始剂量0．2u·kg^-1·d^-1 ,ih,qd。比较两组治疗前后血糖、血糖达标时间、胰岛素用量和低血糖发生率。结果：两组治疗前糖化血红蛋白、血糖及胰岛素分泌差异无统计学意义（P〈0．05）,治疗后血糖均明显下降（P〈0．01）;治疗组较对照组血糖达标时间短（P〈0．01）,胰岛素用量及低血糖发生率均减少（P〈0．05）。结论：地特胰岛素是治疗早期2型糖尿病有效的基础胰岛素。     

甘精胰岛素不同给药时间治疗1型糖尿病的疗效及安全性研究

目的：探讨不同时间皮下注射甘精胰岛素治疗1型糖尿病的疗效及安全性。方法选取50例1型糖尿病患者,应用门冬胰岛素联合甘精胰岛素进行治疗,在甘精胰岛素不改变用量前提下,给药时间由22：00调整到18：00前后,比较时间调整前后3 d患者空腹血糖（ FBG）、早中晚餐后2 h血糖（2hPG）和午餐前血糖的变化情况、门冬胰岛素的用量及午餐前患者低血糖事件发生情况。结果甘精胰岛素调整用药时间后,患者午餐前血糖调整至理想水平,FBG（7．28±2．13）mmol/L比（8．33±2．20）mmol/L、午餐后2hPG下降显著（8．61±2．59）mmol/L 比（9．70±1．75）mmol/L（U＝2．425、3．034,均 P＜0．05）,早餐后2hPG （8．27±2.02）mmol/L比（8．56±2．33）mmol/L和晚餐后2hPG（9．54±1．55）mmol/L比（9．61±1．75）mmol/L变化均不明显（均P＞0．05）;门冬胰岛素早餐前用量减少,午餐前和晚餐前用量增加;午餐前低血糖事件显著减少（χ2＝4．105、5．005,均P＜0．05）。结论甘精胰岛素联合门冬胰岛素治疗1型糖尿病患者,在不改变甘精胰岛素用量情况下,给药时间由22：00调整为18：00,可平稳降低空腹血糖,减少午餐前低血糖的发生。     

Insulin glargine

Insulin glargine is an extended-action biosynthetic human insulin. It precipitates in the neutral environment of subcutaneous tissue and is thus gradually absorbed into the bloodstream. The addition of small amounts of zinc to the formulation further delays absorption. In small euglycaemic clamp studies, the onset of action of insulin glargine was shown to be later, the duration of action longer and the time-action profile flatter than that of Neutral Protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus and healthy volunteers. Four large clinical trials of up to 28 weeks' duration have shown that a single bedtime dose of insulin glargine, in combination with preprandial short-acting insulin, is as effective or more effective than once or twice daily NPH plus short-acting insulin in improving glycaemic control in patients with type 1 diabetes mellitus. In 3 large comparative trials, insulin glargine decreased glycosylated haemoglobin and/or fasting blood glucose levels to a similar extent to that seen with NPH insulin in patients with insulin-dependent or non-insulin-dependent type 2 diabetes mellitus, either as monotherapy or in combination with oral hypoglycaemic agents. Insulin glargine appears to be well tolerated. A lower incidence of hypoglycaemia, especially at night, was reported in most trials with insulin glargine when compared with NPH insulin.