Novo Nordisk announced that the U.S. Food and Drug Administration (FDA) approved the new drug application for Victoza (liraglutide injection), the first once-daily human glucagon-like peptide-1 (GLP-1) analog for the treatment of type 2 diabetes. Victoza is indicated as an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes mellitus.

Victoza was evaluated in The Liraglutide Effect and Action in Diabetes (LEAD) phase III trials, the most comprehensive clinical development program conducted to date by Novo Nordisk in type 2 diabetes. In clinical studies including use as monotherapy and in combination with standard diabetes treatments, Victoza produced significant reductions in A1C and also was associated with weight loss.

"Novo Nordisk is committed to developing safe and effective drugs to treat diabetes, which is why the FDA approval of Victoza represents such an important milestone for the company and for people with type 2 diabetes," says Alan C. Moses, M.D., vice president, and chief global medical officer of Novo Nordisk. "Victoza will be a substantial addition to our diabetes portfolio and we believe many people with type 2 diabetes will benefit from this treatment."

"Maintaining control of blood sugar remains a challenge for many type 2 diabetes patients and without control, patients are at risk of developing serious and life-threatening complications," said Alan J. Garber, MD, PhD, FACE, Professor of Medicine, Biochemistry and Molecular Biology, and Cellular Biology Department of Medicine Baylor College of Medicine Houston, Texas. "The approval of Victoza provides patients a once-daily treatment that not only lowers blood sugar, but unlike many other diabetes therapies, does not promote weight gain and is associated with weight loss in the majority of patients. Additionally, it offers patients an attractive new treatment option that has consistently performed well when compared to other currently available treatments."

The American Diabetes Association and European Association for the Study of Diabetes as well as the American Association of Clinical Endocrinologists and the American College of Endocrinology recently updated their treatment algorithms for type 2 diabetes. The algorithms recommend GLP-1 agonists like Victoza as a viable treatment option when blood sugar goals are not met or maintained with lifestyle adjustments and metformin.

Novo Nordisk expects to introduce Victoza in the U.S. market in 4 - 6 weeks. In addition to the U.S. approval, Victoza has been approved by the European Medicines Agency (EMEA) in all 27 European Union member states, Mexico and Iceland. On January 20th, Victoza was also approved in Japan. A New Drug Application was submitted for China in August 2009, regulatory decision is pending.

Indications and Usage

Victoza is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Victoza is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise. It has not been studied sufficiently in patients with a history of pancreatitis. Victoza should not be used to treat type 1 diabetes mellitus ordiabetic ketoacidosis. It has not been studied in combination with insulin.

About Victoza

Victoza is the first and only human GLP-1 analog with 97% homology to natural GLP-1. Like natural GLP-1, Victoza works by stimulating the beta cells to release insulin only when blood glucose levels are high. Due to this glucose-dependent mechanism of action, Victoza is associated with a low rate of hypoglycemia. The mechanism of blood glucose lowering also involves a delay in gastric emptying.

In clinical studies submitted for FDA review, Victoza's safety and efficacy were evaluated in five trials, one of 52-weeks duration and four of 26-weeks duration. These multinational trials evaluated Victoza in monotherapy as well as in combination with one or two oral anti-diabetic medications and showed better lowering of blood glucose than active comparators such as sulfonylureas and thiazolidinediones. A1C reductions for Victoza 1.8 mg, in combination or as monotherapy, ranged from 1.0% to 1.5% across the five clinical studies with baselines ranging from 8.2% to 8.6%. Victoza 1.8 mg + metformin reduced A1C by 1.0% and reduced weight by 6.2lbs. The most common adverse reactions reported in patients treated with Victoza are headache, nausea, diarrhea, and anti-liraglutide antibody formation. Immunogenicity-related events, including urticaria, were more common among Victoza-treated patients than among comparator-treated patients in clinical trials.

For full prescribing information, please go to Victoza.com or call 1-877-4VICTOZA (1-877-484-2869).

注射用降糖药利拉鲁肽利与弊

作为新一代以肠促胰素为基础的降血糖药物人胰高血糖素样肽-1（GLP-1）类似物――利拉鲁肽（liraglutide）,历经10年研发，终于在2009年7月、2010年1月分别在欧盟和日本上市。2010年1月25日，美国食品与药物管理局（FDA）批准利拉鲁肽在美国上市，并将适应证规定为辅助饮食与运动疗法的、部分成人的2型糖尿病用药，不推荐作为一线用药。　

利拉鲁肽的作用机制　

利拉鲁肽为GLP-1受体激动剂。 GLP-1是人体内存在的一种生理性多肽。它能够根据体内葡萄糖水平高低，按需促进胰岛β细胞分泌胰岛素，抑制胰岛素拮抗激素胰高血糖素的分泌，从而发挥降糖作用。然而，人体产生的GLP-1很不稳定,很快就会被体内的二肽基肽酶Ⅳ（DPP-Ⅳ）降解,若使用天然GLP-1降低血糖,则需持续静脉输注或持续皮下注射。　

利拉鲁肽是一种GLP-1的酰化物，即在天然GLP-1的分子结构上更换了1个氨基酸（第34位的赖氨酸改为精氨酸），并在第26位增加了1个16碳棕榈酰脂肪酸侧链，从而在保留天然GLP-1功效的同时克服了其易降解的缺点。　

利拉鲁肽之利　

通过上述分子改变，利拉鲁肽成为长效药物，仅需每日1次皮下注射就能起到良好的降糖作用，并提供多种降糖以外的益处。　

利拉鲁肽具有优异的降糖效果，无论其单独应用还是与其他口服降糖药联用,均能迅速、高效和持久地降低血糖及糖化血红蛋白水平。由于其具有葡萄糖依赖的降糖机制，利拉鲁肽仅在血糖水平高的时候通过刺激胰岛素释放达到治疗效果，患者出现低血糖症状的概率很低，非常合乎正常生理需要，故被业内人士美称为“智能降糖药”。　

此外,利拉鲁肽能改善β细胞功能、降低血压，显示出了延缓糖尿病进展及减少糖尿病心血管并发症的潜能。与其他大多数抗高血糖药物相比，利拉鲁肽还能减轻患者体重。这种集多种药理作用于一身的特点是现有糖尿病治疗药物所不具备的。许多临床资料也证实，其单药或与其他抗高血糖药并用，疗效均优于格列美脲、格列本脲、二甲双胍、罗格列酮及其与甘精胰岛素的合用等。　

该药安全性好，患者耐受性良好。最常见的不良反应是胃肠道反应,如恶心、腹泻和头痛等。因此,利拉鲁肽被一些临床专家称为“2型糖尿病治疗的划时代药物”。　

利拉鲁肽可能之弊

然而，看事物应该一分为二，在赞誉其优点之时，千万不要忽视其不足。因为药物可能引起的严重不良反应往往在上市后经过大量人群使用才被发现。　

值得注意的是，在研讨利拉鲁肽临床应用时，千万不要忽视FDA在批准该药时明确强调的两点：一是不推荐该药作为一线用药；二是鉴于该药在大鼠和小鼠试验中，曾出现乳头状甲状腺瘤和（或）癌，并在临床试验时曾有引发胰腺炎的病例报告。　

为确保该产品的安全性和有效性，FDA要求生产企业制定包括用药指南与交流计划在内的风险评估与降低计划（EMS），以帮助患者和医师了解该产品安全性方面的相关信息。也就是说，在临床应用利拉鲁肽的过程中，医患均必须时刻警惕甲状腺瘤和（或）癌及胰腺炎的发生。