2015年4月23日,诺和诺德（Novo Nordisk）在美国推出新型减肥药Saxenda（liraglutide，利拉鲁肽，3mg），该药是首个开发用于体重管理的胰高血糖素样肽-1（GLP-1）受体激动剂，已获美国、欧盟、加拿大批准。
Saxenda（利拉鲁肽，3mg）是利用糖尿病药物liraglutide（利拉鲁肽）开发而成的首款减肥药物，该药也是近几年获批的第4款减肥药，也是唯一的减肥针剂。Saxenda的适应症为作为一种辅助药物，联合低热量饮食及运动，用于体质指数（BMI）大于或等于30 的成年人，或者是那些体质指数为27及以上、伴有高血压、2型糖尿病或高胆固醇等至少一种肥胖并发症的成年人。
Saxenda® (liraglutide [rDNA origin] injection) is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).

SAXENDA Rx
Pharmacological Class:
Glucagon-like peptide-1 (GLP-1) receptor agonist.

Active Ingredient(s):
Liraglutide [rDNA origin] 6mg/mL; soln for SC inj.

Company
Novo Nordisk
Indication(s):
Adjunct to reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of ≥30kg/m2 (obese), or ≥27kg/m2 (overweight) in the presence of at least one weight-related comorbid condition (eg, hypertension, T2DM, dyslipidemia). Limitations of use: not indicated for type 2 diabetes. Do not use with Victoza, other GLP-1 receptor agonists, or insulin. Effects on cardiovascular morbidity and mortality have not been established. Safety and efficacy with concomitant other weight loss products has not been established. Not studied in patients with history of pancreatitis.

Pharmacology:
Liraglutide binds to and activates the GLP-1 receptor, a cell-surface receptor coupled to adenylyl cyclase activation through the stimulatory G-protein, Gs.

Clinical Trials:
The safety and efficacy of Saxenda for chronic weight management in conjunction with reduced caloric intake and increased physical activity were studied in three 56-week trials.

Study 1 (n=3731) and Study 3 (n=422) included patients who were obese or overweight and at least one weight-related comorbid condition (eg, dyslipidemia, hypertension). Study 2 (n=635) included patients with type 2 diabetes who were either overweight or obese.

For Study 1 and Study 2, the primary efficacy parameters were mean percent change in body weight and the percentages of patients achieving ≥5% and 10% weight loss from baseline to week 56. For Study 3, the primary efficacy parameters were mean percent change in body weight from randomization to week 56, the percentage of patients not gaining >0.5% body weight from randomization (eg, after run-in) to week 56, and the percentage of patients achieving ≥5% weight loss from randomization to week 56.

After 56 weeks, treatment with Saxenda resulted in a statistically significant reduction in weight compared with placebo. A greater proportion of patients treated with Saxenda achieved 5% and 10% weight loss than those treated with placebo. In Study 3, statistically significantly more patients randomized to Saxenda than placebo had not gained more than 0.5% of body weight from randomization to week 56.

For more clinical trials data, see full labeling.

Legal Classification:
Rx

Adults:
Give by SC inj into abdomen, thigh, or upper arm once daily. Escalate dose gradually. Week 1: 0.6mg daily; Week 2: 1.2mg daily; Week 3: 1.8mg daily; Week 4: 2.4mg daily; Week 5 and onward: 3mg daily. Delay dose escalation 1 week if increased dose not tolerated; discontinue if 3mg not tolerated. If >3 days elapsed since last dose, reinitiate at 0.6mg/day, then titrate. Evaluate response after 16 weeks. Discontinue if ≥4% weight loss is not achieved.

Children:
Not recommended.

Contraindication(s):
History (personal or family) of medullary thyroid carcinoma. Multiple endocrine neoplasia syndrome type 2. Pregnancy (Category X).

Warnings/Precautions:
Inform patients of thyroid cancer risk and symptoms. Monitor for signs/symptoms of pancreatitis; discontinue if suspected; do not restart if confirmed. Risk of acute gallbladder disease. History of suicidal attempts or ideation: avoid. Monitor for emergence or worsening depression, suicidal thinking or behavior; discontinue if occurs. Monitor blood glucose prior to and during treatment in type 2 diabetics. Monitor heart rate periodically; discontinue if sustained increases. History of angioedema with other GLP-1 receptor agonist. Discontinue if hypersensitivity reactions occur. Renal or hepatic impairment. Gastroparesis. Nursing mothers: not recommended.

Interaction(s)
Risk of hypoglycemia with concomitant insulin secretagogues (eg, sulfonylureas); consider reducing their doses by ½. May affect absorption of other oral drugs (delayed gastric emptying).

Adverse Reaction(s)
Nausea, hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase.

How Supplied:
Multi-dose, pre-filled pen (3mL)—3, 5

LAST UPDATED:
5/8/2015

近日，美国FDA批准Saxenda（利拉鲁肽[rDNA来源]注射液）作为一种除低热量饮食及体育活动之外的治疗选择用于慢性体重管理。这款药物被批准用于体重指数(BMI)为30或更大（肥胖）的成年人，或BMI为27或更大（超重）同时伴有至少一种与体重相关疾病如高血压、2型糖尿病或高胆固醇（血脂异常）的成年人。
BMI基于个人的体重和身高来衡量人体的脂肪，这一指标用来定义肥胖和超重的范畴。据美国疾病控制与预防中心称，美国超过三分之一的成年人属于肥胖。
“肥胖是一个公众健康问题，威胁患者的整体健康，”FDA药物评价与研究中心代谢与内分泌部门代理副主任、医学博士、理科硕士Smith称。“Saxenda结合健康的生活方式，包括低热量饮食及锻炼，可以为肥胖或超重及至少伴有一种与体重相关并发症的人提供一种额外治疗选择用于慢性体重管理。”
Saxenda是一种胰高血糖素样肽-1 (GLP-1)受体激动剂，它不应与这一类别的任何其它药物合并使用，包括用于治疗2型糖尿病的Victoza。Saxenda与Victoza含有相同的活性成分利拉鲁肽，但剂量不同，它们的剂量分别为3mg与1.8mg。此外，Saxenda不适用于治疗2型糖尿病，因为Saxenda用于糖尿病治疗的安全性及有效性尚未得到确定。
Saxenda的安全性及有效性在3项由大约4800名肥胖及超重、有或没有明显与体重相关病症患者参与的临床试验中得到评价。所有患者接受与改变生活方式有关的咨询，包括低热量饮食及有规律的体育活动。
一项由未患糖尿病患者参与的临床试验显示，与安慰剂治疗患者相比，Saxenda治疗患者在一年内相比基线体重平均减轻4.5%。在这项试验中，62%的Saxenda治疗患者其体重至少减轻5%，相比之下，以安慰剂治疗患者只有34%的人达到这一结果。
来自另一项由2型糖尿病患者参与的试验结果显示，与安慰剂治疗相比，Saxenda治疗在一年内使患者体重平均减轻3.7%。在这项试验中，49%的Saxenda治疗患者其体重至少减轻5%，相比之下，安慰剂治疗患者只有16%的人达到这一结果。
使用Saxenda的患者应在用药16周后进行评价，以确定这款治疗药物是否在起作用。如果患者基线体重未至少减轻4%，那么应该停止Saxenda用药，因为患者继续使用这款药物达到及保持临床有意义的体重减轻是不太可能的。
Saxenda带有一项黑框警告，提示在Saxenda的啮齿动物研究中观察到有甲状腺瘤（甲状腺C细胞瘤）发生，但尚不清楚Saxenda是否在人身上会引起甲状腺C细胞瘤，包括一种叫做甲状腺髓样癌(MTC)的甲状腺瘤。Saxenda不应用于个人或有MTC家族史的患者，或多发性内分泌瘤综合征2型（一种患者身上出现一种以上腺体瘤的疾病，该疾病使患者倾向于发生MTC）患者。
Saxenda治疗患者中报道的严重副作用有胰腺炎、胆囊疾病、肾功能障碍和自杀念头。Saxenda还可以增加心率，静息心率持续增加的患者应该停止用药。在临床试验中，Saxenda治疗患者观察到的最常见副作用有恶心、腹泻、便秘、呕吐、低血糖(血糖过低)及食欲下降。
FDA要求对Saxenda进行以下上市后研究：
用来评价儿科患者用药剂量、安全性及有效性的临床试验；
用来评价对未成熟大鼠生长、性成熟及中枢神经系统发育与功能潜在影响的一项研究；
一项至少15年期的MTC病例登记，用来证实与Saxenda相关的MTC发病率是否有增长；
在正在进行的临床试验中进行一项与使用Saxenda有关的潜在乳腺癌风险的评价。
此外，利拉鲁肽的心血管安全性研究正在一项心血管结局试验中进行研究。FDA批准Saxenda时带有一项风险评估及减灾策略(REMS)，它包括一项用来告知卫生保健专业人员有关Saxenda相关严重风险的沟通计划。Saxenda由丹麦Bagsvaerd的诺和诺德A/S生产，由新泽西州Plainsboro的诺和诺德分销