ST LOUIS (MD Consult) - On January 26, 2010, Novo Nordisk announced that the US Food and Drug Administration (FDA) has approved Victoza (liraglutide) for the treatment of type 2 diabetes in adults. Victoza is a human glucagon–like peptide-1 analogue and is indicated as an adjunct to diet and exercise to improve glycemic control. It is administered as a once-daily injection. The medication may be used as a monotherapy in second-line treatment for diabetes and in combination with other commonly prescribed oral antidiabetic agents.

Victoza works by stimulating the release of insulin from the pancreatic beta cells when blood glucose levels are elevated. The metabolic breakdown of Victoza is not dependent on renal excretion.

The Victoza phase 3 clinical trial program (Liraglutide Effect and Action in Diabetes [LEAD]), which formed the basis of the regulatory submission to the FDA, is composed of randomized, controlled, double-blinded studies comparing Victoza to commonly prescribed treatments for diabetes. These multinational trials evaluated the use of Victoza alone and in combination with 1 or 2 oral antidiabetic medications. The results indicated that patients receiving Victoza experienced superior or equivalent lowering of blood glucose levels compared with patients receiving active comparators such as sulphonylureas and thiazolidinediones. In addition, clinical trial data demonstrate that patients in the LEAD program experienced a reduction in body weight. (Body weight was a secondary end point in the clinical development trials.)

The most common adverse events reported during the clinical development program in patients treated with Victoza were associated with the gastrointestinal system. Gastrointestinal adverse events, including nausea, vomiting, and diarrhea, were reported most frequently in the early part of the treatment period with Victoza, and few patients withdrew as a result of adverse events.

The prescribing information for Victoza includes a boxed warning about the risk of thyroid C-cell tumors. In preclinical testing, Victoza caused thyroid C-cell tumors in rodents. In clinical trials, no reported cases of medullary thyroid carcinoma (MTC) occurred in patients treated with Victoza, but human relevance of the rodent findings could not be ruled out by clinical or nonclinical studies. Victoza is contraindicated in patients with a personal or family history of MTC or multiple endocrine neoplasia syndrome type 2.

In 5 clinical trials involving more than 3,900 participants, pancreatitis occurred more often in patients who received Victoza than in patients receiving other antidiabetes medications. Victoza should be discontinued in the presence of severe abdominal pain, with or without nausea and vomiting, and should not be restarted if blood test results confirm a diagnosis of pancreatitis. Victoza should be used with caution in persons with a history of pancreatitis.

Victoza has not been associated with an increased risk for cardiovascular events in persons who were mainly at low risk for these events. However, the FDA approved Victoza with several postmarketing requirements to ensure that the manufacturer will conduct studies to provide additional information on product safety. In addition to a cardiovascular safety study to specifically evaluate the use of Victoza in a higher-risk population, Nova Nordisk also is required to conduct a 5-year epidemiologic study using a health-claims database to evaluate thyroid and other cancer risks as well as risks for serious hypoglycemia, pancreatitis, and allergic reactions in patients receiving the drug. To specifically evaluate the risk of medullary thyroid cancer, the company is required to establish a cancer registry to monitor the rate of this type of cancer in the United States over the next 15 years.

 

Victoza is not recommended as initial therapy in patients who have not achieved adequate diabetes control on diet and exercise alone.

 

圣路易斯(MD Consult)——2010年1月26日，诺和诺德公司宣布，美国食品药品管理局(FDA)已批准Victoza (利拉鲁肽)用于治疗2型糖尿病成人患者。Victoza是一种人胰高血糖素样肽1类似物，适用于饮食和运动之外糖尿病患者的辅助治疗以改善血糖控制。该药用法为每日注射1次。该药既可单用作为糖尿病的二线治疗药物，也可与其他常用口服抗糖尿病药联合应用。

Victoza的作用机制在于通过使血糖水平升高而刺激胰岛β细胞分泌胰岛素。Victoza的代谢分解不依赖于肾排泄。

 

Victoza III期临床试验项目，即利拉鲁肽治疗糖尿病的疗效与作用研究(Liraglutide Effect and Action in Diabetes，LEAD)，包括多项比较Victoza与常用抗糖尿病药物的随机对照双盲试验。该项目奠定了向FDA提交药监申报的基础。这些多国试验评价了Victoza单用及与1或2种口服抗糖尿病药联用的情况。结果显示，Victoza组患者血糖降幅大于或等于活性对照药物(如磺脲类药物和噻唑烷二酮类药物)组患者。此外，临床试验数据显示，该LEAD项目中的患者体重出现下降 (体重是这些临床开发试验的次要终点)。

这些临床开发试验中最常见的Victoza治疗相关不良事件是胃肠道不良事件。Victoza治疗早期最常见的胃肠道不良事件包括恶心、呕吐和腹泻。很少有患者因不良事件而退出研究。 

 

Victoza处方信息包含一个有关甲状腺C细胞肿瘤风险的黑框警告。在啮齿动物中进行的临床前试验显示，Victoza可导致甲状腺C细胞肿瘤。在临床试验中，没有患者在接受Victoza治疗后出现甲状腺髓样癌(MTC)，但通过临床或非临床研究无法排除在啮齿动物中发现的结果与人类之间的相关性。Victoza禁用于有MTC或II型多发性内分泌肿瘤综合征个人史或家族史的患者。 

 

5项纳入超过3,900例受试者的临床试验显示，接受Victoza治疗的患者胰腺炎发生率高于接受其他抗糖尿病药治疗的患者。如出现伴或不伴恶性和呕吐的严重腹痛，应停用Victoza。如血液检查结果证实胰腺炎诊断，就不应再次使用Victoza。Victoza应慎用于有胰腺炎病史的患者。

在总体上心血管事件风险较低的患者中，Victoza不会增加这些事件的风险。但是，FDA在批准Victoza的同时对生产厂家提出了几项上市后要求，以确保其开展上市后研究，提供有关产品安全性的进一步信息。诺和诺德公司除了需要进行一项专门评价Victoza在高危人群中应用情况的心血管安全性研究之外，还需采用医疗保险理赔数据库进行一项为期5年的流行病学研究，在该药治疗患者中评价发生甲状腺癌和其他癌症的风险以及发生严重低血糖、胰腺炎和过敏反应的风险。为了专门评价甲状腺髓样癌风险，该公司需建立一个癌症登记库，以监测未来15年美国国内此类癌症的发生率。

对于经单纯饮食和运动治疗糖尿病未获充分控制的患者，不建议使用Victoza作为初始治疗药物。