度拉糖肽Trulicity(dulaglutide)一种一周1次皮下注射剂
Pharmacological Class:
Glucagon-like peptide-1 (GLP-1) receptor agonist.

Active Ingredient(s):
Dulaglutide 0.75mg/0.5mL, 1.5mg/0.5mL; solution for SC injection; pen or prefilled syringe.

Company
Lilly, Eli and Company
Indication(s):
Adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes. Limitations of use: not recommended as first-line treatment for patients inadequately controlled on diet and exercise. Not studied in combination with basal insulin or with history of pancreatitis. Not for treating type 1 diabetes or diabetic ketoacidosis. Not a substitute for insulin. Not recommended in patients with pre-existing severe GI disease.

Pharmacology:
Trulicity activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. It increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying.

Clinical Trials:
Trulicity has been studied as monotherapy and in combination with metformin, metformin + sulfonylurea, metformin + thiazolidinedione, and prandial insulin ± metformin.

In a 52-week double-blind study, patients inadequately treated with diet and exercise, or with diet and exercise and one antidiabetic agent at submaximal dose, were randomized to receive Trulicity 0.75mg once weekly (n=270), Trulicity 1.5mg once weekly (n=269), or metformin 1500–2000mg daily (n=268) after a 2-week washout.

Treatment with Trulicity 0.75mg and 1.5mg once weekly resulted in reduction of HbA1c from baseline at the 26-week primary time point. The Trulicity 0.75mg and 1.5mg treatment groups showed a −0.7% and −0.8% change from baseline HbA1c (adjusted mean), respectively, vs. a −0.6% change in the metformin treatment group.

Both the Trulicity 0.75mg and 1.5mg treatment groups also had a −26mg/dL and −29mg/dL change from baseline fasting serum glucose, respectively, vs. a −24mg/dL change in the metformin group.

In a 104-week placebo-controlled, double-blind study, patients were randomized to placebo (n=139), Trulicity 0.75mg once weekly (n=281), Trulicity 1.5mg once weekly (n=279), or sitagliptin 100mg daily (n=273) after an 11-week lead-in and a 6-week stabilization period, all as add-on to metformin. At the 26 week placebo-controlled time point, the HbA1c reduction was 0.1%, 1.0%, 1.2%, and 0.6% for placebo, Trulicity 0.75mg, Trulicity 1.5mg, and sitagliptin, respectively. Treatment with Trulicity 0.75mg and 1.5mg once weekly resulted in a statistically significant reduction in HbA1c (−0.9%, −1.1%, respectively) vs. placebo at Week 26 and vs. sitagliptin (−0.4%) at Weeks 26 and 52, all in combination with metformin.

For more clinical trials data, see full labeling.

Legal Classification:
Rx

Adults:
Give by SC inj in the abdomen, thigh, or upper arm any time of the day, with or without food. ≥18 years: initially 0.75mg once weekly; may increase to max 1.5mg once weekly if inadequate response. Renal impairment: caution with initiating or escalating doses.

Children:
<18 years: not established.

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

Warnings/Precautions:
Inform patients of thyroid cancer risk and symptoms. Monitor for pancreatitis; discontinue if suspected; do not restart if confirmed. History of pancreatitis; consider other antidiabetic therapies. Discontinue if hypersensitivity occurs. Monitor renal function in renally-impaired patients reporting severe GI reactions. Hepatic impairment. Pregnancy (Category C). Nursing mothers: not recommended.

Interaction(s)
Increased risk of hypoglycemia with concomitant sulfonylureas or insulin; consider reducing their doses. May affect absorption of other oral drugs (delayed gastric emptying).

Adverse Reaction(s)
Nausea, diarrhea, vomiting, abdominal pain, decreased appetite, dyspepsia; acute pancreatitis.

How Supplied:
Single-dose pen—4; Single-dose prefilled syringe—4

LAST UPDATED:
11/21/2014


2014年9月18日美国食品药品监督管理局(FDA)批准Trulicity(dulaglutide)，一种一周1次皮下注射剂在有2型糖尿病成年中与饮食和锻炼一起改善血糖控制(血液水平)。
Trulicity是一种胰高血糖素样肽-1(GLP-1)受体激动剂，一种帮助血糖水平正常化的激素。在6项临床试验其中3,342例有2型糖尿病患者接受Trulicity评价药物的安全性和有效性。患者接受Trulicity有其血糖控制改善如观察到有HbA1c水平减低(血红蛋白A1c是血糖控制的一种测量)。
Trulicity曾被研究作为一种单药治疗和与其他2型糖尿病治疗联用，包括二甲双胍，磺脲类，噻唑烷二酮类，和餐时胰岛素。Trulicity不应被使用治疗1型糖尿病人们；血或尿中酮体增加患者(糖尿病酮体酸中毒)；有严重胃或小肠问题患者；或对不能用饮食和锻炼处理作为一线治疗的患者。
Trulicity有一个黑框警告，在啮齿类用Trulicity研究中曾观察到甲状腺(甲状腺C-细胞肿瘤)但不知道Trulicity是否在人类中致甲状腺C-细胞肿瘤，包括一类型甲状腺癌被称为甲状腺髓样癌(MTC)。在以下情况不应使用Trulicity：有个人或家庭MTC病史患者或在有多发性内分泌腺瘤综合征2型患者(一种疾病其中患者机体内1个以上腺体内有肿瘤，使他们容易诱发MTC)。
FDA正在要求对Trulicity进行以下上市后研究：
⑴在儿童患者中一项临床试验评价给药，疗效，和安全性；
⑵在不成熟大鼠中一项研究评估对性成熟，生殖，和CNS发育和功能的潜在影响；
⑶一项髓性甲状腺癌(MTC)病例注册至少15年时间以减低与Trulicity相关MTC发生率的任何增加；
⑷在有2型糖尿病患者和中度或严重肾受损患者中一项临床试验比较Trulicity与甘精胰岛素[insulinglargine]对血糖控制；和
⑸一项心血管结局试验以评价在有高心血管疾病基线风险患者中Trulicity的心血管风险。
FDA批准的Trulicity有一个风险评估和减低策略(REMS)，其中包括交流计划告知卫生保健专业人员关于伴随Trulicity严重风险。
在临床试验中，用Trulicity治疗患者中最常观察到的副作用是恶心，腹泻，呕吐，腹痛，和食欲减低.