每日3次诺和锐30治疗2型糖尿病疗效观察

目的 比较不同胰岛素强化治疗对T2DM的疗效.方法 240例T2DM患者随机分为两组:诺和锐30组(124例)日3次诺和锐30皮下注射;诺和灵组(116例)日4次重组人胰岛素治疗(三餐前半小时注射诺和灵R,睡前注射诺和灵N).结果 两组相比,诺和锐30组控制血糖更快,胰岛素用量更少,低血糖发生率更低.结论 日3次注射诺和锐30,能更有效控制血糖,但需警惕低血糖发生.     

Insulin therapy in type 2 diabetes patients failing oral agents: cost-effectiveness of biphasic insulin aspart 70/30 vs. insulin glargine in the US

OBJECTIVES: To project the long-term clinical and economic outcomes of treatment with biphasic insulin aspart 30 (BIAsp 70/30, 30% soluble and 70% protaminated insulin aspart) vs. insulin glargine in insulin-na?ve type 2 diabetes patients failing to achieve glycemic control with oral antidiabetic agents alone (OADs). METHODS: Baseline patient characteristics and treatment effect data from the recent 'INITIATE' clinical trial served as input to a peer-reviewed, validated Markov/Monte-Carlo simulation model. INITIATE demonstrated improvements in HbA1c favouring BIAsp 70/30 vs. glargine (-0.43%; p < 0.005) and greater efficacy in reaching glycaemic targets among patients poorly controlled on OAD therapy. Effects on life expectancy (LE), quality-adjusted life expectancy (QALE), cumulative incidence of diabetes-related complications and direct medical costs (2004 USD) were projected over 35 years. Clinical outcomes and costs were discounted at a rate of 3.0% per annum. Sensitivity analyses were performed. RESULTS: Improvements in glycaemic control were projected to lead to gains in LE (0.19 +/- 0.24 years) and QALE (0.19 +/- 0.17 years) favouring BIAsp 70/30 vs. glargine. Treatment with BIAsp 70/30 was also associated with reductions in the cumulative incidences of diabetes-related complications, notably in renal and retinal conditions. The incremental cost-effectiveness ratio was $46 533 per quality-adjusted life year gained with BIAsp 70/30 vs. glargine (for patients with baseline HbA1c >/= 8.5%, it was $34 916). Total lifetime costs were compared to efficacy rates in both arms as a ratio, which revealed that the lifetime cost per patient treated successfully to target HbA1c levels of <7.0% and 相似文献   

双相门冬胰岛素强化治疗对初诊2型糖尿病患者胰岛β细胞功能的影响

目的观察预混双相门冬胰岛素30(BIAsp30)对初诊2型糖尿病患者血糖控制及其对胰岛β细胞功能的影响。方法对122例初诊2型糖尿病患者,分为BIAsp30治疗组和口服降糖药(OHD)治疗组,治疗6个月,检测两组中层得治疗前后空腹及75克葡萄糖负荷后血糖、胰岛素、C肽、糖化血红蛋白(HbA1c)、胰岛β细胞功能指数(△I/△G)、胰岛素抵抗指数(HomaIR)等指标,比较两组患者血糖控制及胰岛β细胞功能恢复情况。结果BIAsp30和OHD具有降低血糖、改善胰岛β细胞功能的作用,治疗前后比较,差异有非常显著性(P<0.01);两组之间比较,BI-Asp30组在改善患者胰岛β细胞功能、降低胰岛素抵抗方面,明显优于OHD组(P<0.01),且血糖达标所需时间短于OHD组,差异有非常显著性(P<0.01)。结论对新诊断的2型糖尿病患者,早期给予每日两次注射BIAsp30强化治疗能更好的控制血糖,改善和恢复胰岛β细胞功能、降低胰岛素抵抗。     

Starting patients with type 2 diabetes on insulin therapy using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin

Transitioning safely to insulin therapy when oral antidiabetic agents fail to provide adequate glycemic control is a critical aspect of care for the patient with type 2 diabetes mellitus (T2DM). We evaluated the clinical effectiveness of starting patients on a relatively simple regimen of once-daily injections of either biphasic insulin aspart 70/30 (10 min before dinner), NPH insulin (at 10 p.m.), or biphasic human insulin 70/30 (30 min before dinner) in combination with metformin. Enrolled patients had T2DM and inadequate glycemic control (AlC≥7.5%) on a previous regimen of metformin as monotherapy or in combination with a sulphonylurea. One hundred and forty (140) patients received metformin monotherapy for 4 weeks followed by 12 weeks of combination treatment with metformin and once-daily insulin injections. AlC levels decreased from baseline by 1.1–1.3% for patients in each of the three treatment groups. Overall, FPG values decreased from baseline by 31% (biphasic insulin aspart), 37% (NPH insulin), and 28% (biphasic human insulin). Subjects whose final FPG level was <126 mg/dl experienced the largest decreases in AlC values (−2.3%, −1.9%, −1.8%, respectively). All three treatment regimens were well tolerated. The results indicate that patients with T2DM can safely and effectively begin insulin therapy using once-daily injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH insulin in combination with metformin.     

Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin aspart and insulin glargine in people with type 2 diabetes

Aims/hypothesis The pharmacokinetic and pharmacodynamic properties of biphasic insulin aspart (BIAsp 30) (30% soluble, 70% protaminated insulin aspart [IAsp]) and insulin glargine (IGlarg) were compared.Methods Twelve people with type 2 diabetes took part in two 24-h isoglycaemic clamp studies, 1 week apart. Patients were randomised to treatment with 0.5 U/kg of BIAsp 30 (0.25 U/kg at 08.30 h and 0.25 U/kg at 20.30 h) or 0.50 U/kg IGlarg at 08.30 h. Both insulins were given by subcutaneous injection into the anterior abdominal wall. The plasma glucose, glucose infusion rates, plasma insulin and C-peptide concentrations were measured.Results All 12 patients were men; mean (±SD) age was 58.8 (8.9) years, BMI 31.0 (3.0) kg/m² and HbA_1c 7.1 (0.6)%. Plasma glucose was constant throughout the 24-h clamp period. After each injection of BIAsp 30, glucose infusion rates increased, reaching a distinct peak approximately 3–5 h after injection. A much flatter postinjection profile was observed following IGlarg administration. Plasma insulin concentrations rose rapidly after each injection of BIAsp 30, reaching a distinct peak after approximately 2–3 h. A flatter plasma insulin profile reached a plateau approximately 6–16 h after IGlarg administration. Plasma C-peptide fell below baseline after both injections of BIAsp 30 but remained unaltered after IGlarg injection.Conclusions/interpretation The pharmacodynamic and pharmacokinetic profiles were 34 and 28%, respectively, higher following equivalent doses (0.5 U/kg) of BIAsp 30 given as two split doses than following IGlarg given as a single daily dose.     

Postprandial versus preprandial dosing of biphasic insulin aspart in elderly type 2 diabetes patients

Preprandial dosing (within 5 min before meal) and postprandial dosing (15-20 min after meal onset) of NovoLog Mix 70/30 (BIAsp 30, a biphasic formulation of insulin aspart, 30% soluble and 70% protamine-crystallized) were compared in elderly (> or =65 years) type 2 diabetes patients in this open-label, 12-week, crossover study. Ninety-three patients were treated with b.i.d. preprandial injections of BIAsp 30 during a 2-week run-in period and subsequently randomized to a 4-week treatment with either pre- or postprandial b.i.d. BIAsp 30, followed by crossover to the other regimen for 4 weeks. Mean plasma glucose values during a 4-h mealtest at the end of each treatment were similar for pre- and postprandial BIAsp 30 (153 +/- 58 mg/dl and 161 +/- 59 mg/dl, respectively, difference not significant). However, the mean blood glucose increment from self-measured blood glucose values was slightly but significantly greater after postprandial injection than after preprandial injection (treatment difference: 16.3mg/dl; 95% CI: [0.5, 29.3]). Fifty-six percent of patients reported a hypoglycemic episode; postprandial injection did not increase the incidence of hypoglycemia as compared to preprandial injection (113 episodes versus 125 episodes, respectively). For some elderly type 2 diabetes patients, postprandial injection of BIAsp 30 may be an acceptable alternative to standard preprandial injection.     

Long-term efficacy and safety of biphasic insulin aspart in patients with type 2 diabetes

BACKGROUND: In this study, we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 (BIAsp30) with that of biphasic human insulin 30 (BHI30) over a period of 24 months in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes (n=125) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a randomized, controlled, multinational trial. RESULTS: No significant difference was found in mean HbA(1c) after 24 months [BIAsp30, 8.35+/-0.20%; BHI30 8.13+/-0.16%; adjusted mean difference (BIAsp30-BHI30) 0.03 (90% CI -0.29 to 0.34)%, P=0.89]. The proportion of patients experiencing major hypoglycaemia was also similar during the first year (BIAsp30, 5%; BHI30, 8%; P=0.72), but it was significantly lower with BIAsp30 than with BHI30 during the second year (BIAsp30, 0%; BHI30, 10%; P=0.04). The proportion experiencing minor hypoglycaemia was not significantly different. No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months (BIAsp30, 4.87+/-1.92%; BHI30; 1.00+/-1.66%; P=0.13). Body weight change was 0.05+/-0.81 kg in the BIAsp30 group and 2.00+/-0.69 kg in the BHI30 group (P=0.07). CONCLUSIONS: Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA(1c) levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes.     

Improved glycaemic control of thrice-daily biphasic insulin aspart compared with twice-daily biphasic human insulin; a randomized, open-label trial in patients with type 1 or type 2 diabetes

Aim:  This trial evaluated the potential for improving glycaemic control by intensifying a conventional twice-daily therapy with premixed human insulin (HI) to a thrice-daily regimen using premixed formulations of biphasic insulin aspart (BIAsp) in patients with type 1 or type 2 diabetes.
Methods:  This was a multicentre, open-label, parallel group trial. After a 4-week run-in period, patients were randomized 1 : 1 to 16 weeks of treatment. A total of 748 patients were screened, 664 were exposed to trial drug and 604 completed the trial.
Results:  Haemoglobin A_1c, the primary efficacy endpoint, was shown to be significantly lower for the BIAsp treatment group compared with the biphasic HI (BHI) 30 group [estimated mean difference: −0.32, 95% confidence interval (CI) (−0.48; −0.16), p = 0.0001]. The average blood glucose level was significantly lower in the BIAsp group [estimated mean difference: −0.79, 95% CI (−1.17; −0.40), p = 0.0001]. There were few major hypoglycaemic episodes, 11 in the BIAsp group and 7 in the BHI 30 group. Although intensification of insulin therapy with BIAsp three times a day was associated with a higher risk of minor hypoglycaemia (relative risk = 1.58, p = 0.0038), the overall rate of minor hypoglycaemia remained low with both the BIAsp and the BHI treatments (13.1 vs. 8.3 episodes/patient year respectively). Overall safety and patient satisfaction were similar with the two insulin therapies.
Conclusions:  This trial confirmed that a thrice-daily BIAsp regimen can safely be used to intensify treatment for patients inadequately controlled on twice-daily BHI. A treat-to-target trial is required to explore the full potential of the BIAsp regimens and evaluate their use as a viable alternative to intensification with a basal-bolus regimen.     

双时相门冬胰岛素30每日1次对2型糖尿病患者的疗效和安全性

目的 评价2型糖尿病患者每日1次应用双时相门冬胰岛素30治疗的有效性和安全性.方法 本研究为多中心、开放性、自身对照的临床观察性研究.2008年9月至2009年6月选取未接受降糖治疗或既往口服降糖药治疗血糖控制效果欠佳的2型糖尿病患者621例,平均年龄（56±11）岁,平均糖尿病病程（4.4±4.2）年（0～30年）,平均体重指数（25.5±2.9）kg/m2,平均糖化血红蛋白（HbA1c）8.5%±1.2%.使用每日1次双时相门冬胰岛素30,起始剂量和最终剂量分别为（0.16±0.05）U/kg、（0.20±0.07）U/kg.联合口服药治疗12周后评价其有效性和安全性,并探索不同基线因素对于疗效的影响.结果 治疗12周后,HbA1c下降了1.8%±1.1%.HbA1c＜6.5%的患者占30.8%,HbA1c＜7%的患者占65.5%.空腹血糖和餐后血糖均显著下降,8时点血糖平均值下降了（3.8±2.3）mmol/L.分别按基线糖尿病病程、HbA1c、注射时间和体重指数分层的分析结果显示,HbA1c达标率随着糖尿病病程的延长和HbA1c的升高而降低.在双时相门冬胰岛索30治疗中,非重度低血糖事件每年每例患者的发生率为1.83次.仅有1例（0.2%）患者发生1次重度（夜间）低血糖事件.患者治疗后体重较治疗前显著降低（P=0.0053）.结论 在未使用降糖治疗或已用口服降糖药但血糖控制不佳的2型糖尿病患者中,双时相门冬胰岛素30每日1次治疗作为胰岛素起始方案,可安全有效地降低血糖水平,尤其适用于HbA1c水平轻至中度升高,病程相对较短的患者.     

Biphasic insulin aspart 30 plus metformin: an effective combination in type 2 diabetes

AIM: This study compared glycaemic control achieved with biphasic insulin aspart 30 (BIAsp 30) monotherapy, BIAsp 30 plus metformin and glibenclamide plus metformin in patients with type 2 diabetes not adequately controlled with metformin. METHODS: In this multinational, open-labelled, parallel group, 16-week trial, 341 patients (patients not adequately controlled with metformin for at least 1 month) with type 2 diabetes were studied. Patients were randomized to receive BIAsp 30, twice daily (n = 107 exposed to treatment), or BIAsp 30, twice daily, plus metformin (n = 108) or glibenclamide plus metformin (n = 114). The primary endpoint was HbA(1c) at end of trial; adverse events, hypoglycaemia episodes, blood lipids and weight were also monitored. RESULTS: In the total population (HbA(1c) 7.5-13.0% at screening), end-of-trial HbA(1c) levels were lower in patients receiving BIAsp 30 plus metformin compared with those receiving BIAsp 30 only [mean treatment difference (+/-s.e.m), 0.39 +/- 0.15%, p = 0.007]. In a subpopulation (HbA(1c) > or = 9.0% at baseline, n = 193), patients receiving BIAsp 30 plus metformin had significantly lower HbA(1c) levels at the end of the trial compared with those receiving glibenclamide plus metformin (treatment difference, 0.46 +/- 0.21%, p = 0.027). Mean body weight (+/-s.d) at the end of the trial was significantly lower in patients receiving glibenclamide plus metformin compared with those receiving BIAsp 30 only (84.3 +/- 13.3 kg vs. 88.9 +/- 16.9 kg, p < 0.001). No major hypoglycaemic episodes were recorded during the trial, and incidence rates for minor and symptoms-only hypoglycaemia were low and similar between treatment groups (0.03-0.04 events/patient/week). CONCLUSION: BIAsp 30 added to metformin could be an appropriate therapeutic option for achieving good glycaemic control, compared with the addition of a second oral agent, particularly where HbA(1c) > or = 9%.     

Multiple mealtime administration of biphasic insulin aspart 30 versus traditional basal-bolus human insulin treatment in patients with type 1 diabetes

AIM: The aim of this study was to compare the effect of multiple mealtime injections of biphasic insulin aspart 30 (30% fast-acting insulin aspart in the formulation, BIAsp30) to traditional basal-bolus human insulin regimen (HI) on glycaemic control in patients with type 1 diabetes. METHODS: Twenty-three patients (eight women and 15 men) aged 44.8 (20.6-62.5) years (median and range) with a diabetes duration of 19.5 (1.6-44.6) years completed the study. All eligible patients were randomly assigned to BIAsp30 thrice daily supplied with bedtime NPH insulin when necessary, or basal-bolus HI for 12 weeks and then switched to the alternative regimen for another 12 weeks. The insulin dose adjustments were made by patients on the basis of advice from a diabetes nurse. At end of each treatment period, the patients attended two profile days, 1 week apart for pharmacodynamic and pharmacokinetic assessments. HbA1C was measured at baseline and at the end of each treatment period. A seven-point self-monitored blood glucose (SMBG) was obtained twice weekly. RESULTS: In comparison with HI, multiple mealtime injections of BIAsp30 resulted in a significant reduction in HbA1C[HI vs. BIAsp30 (%, geometric mean and range): 8.6 (7.4-11.4) vs. 8.3 (6.7-9.8), p = 0.013]. During treatment with BIAsp30, nighttime glycaemic control was significantly improved. Day-to-day variation in pharmacodynamics and pharmacokinetics and the rate of hypoglycaemia were not increased with BIAsp30 compared with HI. Conclusions: In type 1 diabetics, multiple mealtime administration of BIAsp30 compared with traditional basal-bolus human insulin treatment significantly improves long-term glycaemic control without increasing the risk of hypoglycaemia. Despite a higher proportion of intermediate-acting insulin, thrice-daily injections with BIAsp30 do not increase the day-to-day variations in insulin pharmacokinetics and pharmacodynamics.     

Indirect comparison of efficacy and safety of insulin glargine/lixisenatide and insulin degludec/insulin aspart in type 2 diabetes patients not controlled on basal insulin

BackgroundFixed-dose combinations of insulin glargine/lixisenatide (IGlarLixi) or insulin degludec/insulin aspart (IDegAsp) constitute treatment intensification in type 2 diabetes mellitus (T2D).ObjectivesCompare efficacy and safety of IGlarLixi and IDegAsp (as intensification from basal insulin), by indirect comparison of phase III trials, in the absence of head-to-head trials.Study eligibility criteriaStudies comparing treatment intensification by once-daily IDegAsp or IGlarLixi to basal insulin. Data were extracted from two trials (BOOST: Intensify-Basal and LixiLan-L) retained for analysis.Synthesis methodsTreatments were compared in terms of estimated treatment difference (ETD) in glycated haemoglobin (HbA1c), fasting and postprandial plasma glucose (FPG and PPG) change from baseline; in addition to hypoglycaemia incidence and weight changes.ResultsIn a fixed-effect model examining HbA1c control, IGlarLixi was more effective than IDegAsp in reducing HbA1c (ETD 0.53%, P < 0.0001]), PPG (ETD 2.65%, P < 0.0001), and body weight (ETD 1.73 kg, P < 0.0001). Patients on IGlarLixi were more likely to achieve HbA1c < 7% than patients on IDegAsp (odds ratio [OR] = 0.40, P < 0.0001), with lower incidence of hypoglycaemia (OR = 1.33, P < 0.001).LimitationsLimited number of studies; different baseline HbA1c and FPG.ConclusionOnce-daily IGlarLixi is more efficient than once-daily IDegAsp in controlling HbA1c and PPG and associates with greater weight loss and lower hypoglycaemia incidence.     

甘精胰岛素与双相门冬胰岛素用于初诊2型糖尿病患者胰岛素泵治疗后的疗效比较

目的比较甘精胰岛素（来得时）和双相门冬胰岛素（诺和锐30）皮下注射应用于初诊T2DM短期持续皮下胰岛素输注（CSII）治疗后的疗效。方法60例初诊T2DM患者应用CSII治疗后,随机分为以诺和锐30治疗的BIAsp30组和以来得时治疗的Lantus组。比较两组7个时点血糖、HbA1c、低血糖事件及其他不良事件的差异。结果与BIAsp30组相比,Lantus组20周后三餐后血糖水平明显降低,低血糖事件发生次数低（P均〈0．05）;两组FPG、HbA1c及不良事件差异无统计学意义（P均〉0．05）。结论初诊T2DM患者CSII治疗所用Ins剂量相同且血糖达标后,采用来得时睡前1次注射,比早、晚餐前诺和锐30皮下注射治疗者全天血糖控制满意,且低血糖事件发生率低。