诺和诺德IDegLira III期试验显著改善血糖控制及体重

诺和诺德（Novo Nordisk）12月3日公布了实验性糖尿病复方药IDegLira（长效胰岛素degludec/liraglutide[利拉鲁肽]，Victoza/Tresiba）III期研究（Dual II）的数据，该项研究表明，与长效胰岛素degludec相比，IDegLira实现了卓越的血糖水平（HbA1c）控制。在整天及三餐前后，IDegLira改善了空腹血糖和餐后血糖水平，同时还提供了显著的减肥作用。该项研究中，2个治疗组低血糖发生率均较低。该项研究的目的是评估IDegLira中成分liraglutide（利拉鲁肽）对血糖控制的贡献。

IDegLira是有史以来首个每日一次的长效基础胰岛素和胰高血糖素样肽1（GLP-1）类似物的复方药物。

DUAL II研究的数据如下：

-IDegLira治疗组HbA1c水平平均下降1.9%，胰岛素degludec治疗组HbA1c平均下降0.89%（估计治疗差异：-1.05% [95% CI：-1.25至-0.84]，p＜0.0001）。IDegLira使HbA1c从8.7%的基线水平降低至实验结束后的6.9%。

-IDegLira治疗组体重平均下降2.7公斤，胰岛素degludec治疗组体重未变化（估计治疗差异：-2.51公斤[95% CI：-3.21至-1.82]，p＜0.0001）。

-低血糖发生率在2个治疗组相当（IDegLira ：degludec = 24% ：25%），在等量胰岛素剂量时，与degludec相比，IDegLira表现出了优越的血糖控制，同时低血糖风险相当。IDegLira治疗组和degludec治疗组，每位患者确诊低血糖事件发生率分别为1.5 vs 2.6（p=0.13）。

-IDegLira通过降低空腹血糖（FPG）和餐后血糖（PPG），提供了卓越的血糖控制。9点血糖数据（Nine-point glucose profiles）表明，IDegLira治疗组血浆葡萄糖水平显著低于degludec治疗组（7.5 vs 8.7 mmol/L，估计治疗差异：-1.07 mmol/L [95% CI：-1.44至-0.70]，p＜0.0001）。

此外，在DUAL II研究中，IDegLira耐受性良好，因任何不良事件停药率为1.0%。

关于DUAL临床项目：

DUAL I（约1600人）：是一项为期26周、随机、开放标签试验，在经二甲双胍（metformin）或二甲双胍和吡格列酮（pioglitazone）治疗血糖水平控制不足的2型糖尿病患者中开展，将IDegLira、长效胰岛素degludec、利拉鲁肽（liraglutide）进行了疗效和安全性对比。

DUAL II（约400人）：是一项为期26周、随机、双盲、试验，在经基础胰岛素联合二甲双胍±磺脲类（sulphonylurea）/格列奈类（glinides）治疗血糖水平控制不足的2型糖尿病患者中开展，将IDegLira和degludec进行了比较。该项研究的目的是，调查EDegLira中成分利拉鲁肽（liraglutide）对血糖控制的贡献。

关于IDegLira（degludec/liraglutide）：

IDegLira是由长效胰岛素degludec（Tresiba）和liraglutide（利拉鲁肽，Victoza）组成。其中，degludec是每日一次的基础胰岛素，liraglutide是每日一次的GLP-1类似物。对于经基础胰岛素治疗血糖水平不受控制的2型糖尿病患者，每日一次的IDegLira使糖化血红蛋白（HbA1c）显著降低了1.9%，平均体重下降了2.7公斤，同时低血糖发生率与degludec相当。

目前，IDegLira正处于III期临床开发，诺和诺德已于2013年5月向欧盟提交了监管文件.

英文原文：IDegLira demonstrates superior glycaemic control and weight loss with a low rate of hypoglycaemia for patients uncontrolled on basal insulin*

Copenhagen, Denmark, 3 December 2013 – Today, new phase 3 data from the investigational therapy IDegLira (insulin degludec [Tresiba®]/liraglutide injection [Victoza®]) were presented at the World Diabetes Congress of the International Diabetes Federation. The DUAL™ II trial shows that in comparison with insulin degludec, IDegLira achieved superior control of blood sugar levels (HbA1c). Improved fasting and postprandial plasma glucose levels were seen with IDegLira throughout the day and across meals, while providing significant weight loss for adults with type 2 diabetes uncontrolled on basal insulin. The rate of hypoglycaemia was low in both treatment groups, even with a significant difference in HbA1c reduction with IDegLira. This trial was designed to evaluate the contribution of the liraglutide component of IDegLira on glycaemic control.1

IDegLira is the first-ever once-daily, single administration combination of a long-acting basal insulin and glucagon-like peptide 1 (GLP-1) analogue being developed by Novo Nordisk.

"Many patients are concerned about insulin-based therapies due to a fear of weight gain and hypoglycaemia. In the DUAL II trial, IDegLira demonstrated spectacular HbA1c reductions with a weight loss of 2.7 kg for patients uncontrolled on basal insulin. To achieve this, with a low rate of hypoglycaemia and few gastrointestinal adverse effects, is fantastic for this patient population," said Professor John Buse, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

The DUAL™ II trial evaluated IDegLira in people with type 2 diabetes who were uncontrolled on basal insulin at 26 weeks.1

At 26 weeks, once-daily IDegLira provided a mean HbA1C reduction of 1.90% compared with a reduction of 0.89% for people taking insulin degludec (estimated treatment difference: -1.05% [95% confidence interval (CI) -1.25 to -0.84], p<0.0001) at equivalent insulin doses. This resulted in people on IDegLira reaching an HbA1c of 6.9% at the end of the trial from a baseline of 8.7%.
People with type 2 diabetes on IDegLira experienced a significant mean weight loss of 2.7 kg from baseline compared with no weight change with insulin degludec (estimated treatment difference: -2.51 kg [95% CI -3.21 to -1.82], p<0.0001).
Hypoglycaemia incidence was comparable between the two groups (24% for IDegLira vs 25% for insulin degludec), demonstrating that with IDegLira, superior glycaemic control was achieved in comparison with insulin degludec at equivalent insulin doses, with no higher risk of hypoglycaemia. The rates of confirmed hypoglycaemic events per person were 1.5 for IDegLira vs 2.6 for insulin degludec (p=0.13).
IDegLira provides glycaemic control by reducing both fasting plasma glucose (FPG) and postprandial plasma glucose (PPG). Nine-point glucose profiles revealed significantly lower mean plasma glucose with IDegLira compared with insulin degludec (7.5 vs 8.7mmol/L, respectively; estimated treatment difference: -1.07 mmol/L [95% CI -1.44 to -0.70], p<0.0001).
IDegLira was well tolerated with a discontinuation rate of 1.0% at the end of treatment due to any adverse events in DUAL™ II.2 None of the people taking IDegLira who had previously been on basal insulin discontinued due to nausea.2 Overall, gastrointestinal events were low and only marginally higher with IDegLira compared with insulin degludec (nausea 6.5% vs 3.5%; vomiting 3.5% vs 0.0%).1

About the DUAL™ clinical programme

DUAL™ (DUal Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) consists of two phase 3a trials encompassing around 2,000 people with type 2 diabetes.

DUAL™ I (around 1,600 people) – a 26-week, randomised, open-label trial comparing the efficacy and safety of IDegLira, insulin degludec and liraglutide, in people with type 2 diabetes inadequately controlled with metformin with or without pioglitazone.

DUAL™ II (around 400 people) – a 26-week, randomised, double-blinded trial comparing IDegLira and insulin degludec in people with type 2 diabetes uncontrolled on basal insulin in combination with metformin ± sulphonylurea/glinides. Sulphonylureas and glinides were discontinued at randomisation. In this trial, the allowed maximum dose of insulin degludec in the treatment arms was 50 units to investigate the contribution of the liraglutide component of IDegLira on glycaemic control.

About IDegLira (insulin degludec/liraglutide)

IDegLira is a combination of insulin degludec (Tresiba®), a once-daily basal insulin analogue with an ultra-long duration of action, and liraglutide (Victoza®), the once-daily human GLP-1 analogue for the treatment of type 2 diabetes, which is being developed for the treatment of type 2 diabetes. For people with type 2 diabetes uncontrolled on basal insulin therapy, once-daily IDegLira has demonstrated a significant reduction in HbA1C of 1.9% with a mean weight loss of 2.7 kg with a low rate of hypoglycaemia comparable to that of insulin degludec. IDegLira was administered once daily independently of meals and has shown consistent results in both insulin-naïve people as well people with type 2 diabetes that are uncontrolled on basal insulin. IDegLira is being investigated in a phase 3 clinical trial programme, DUAL™. Novo Nordisk submitted the regulatory filing for IDegLira in the EU on 31 May 2013.