FDA批准Amylin公司普兰林肽(pramlintide,Symlin)用于糖尿病
3月17日，FDA批准Amylin公司的普兰林肽（pramlintide，Symlin）注射剂用于成人1型和2型糖尿病。本品是一合成激素，也是至今为止继胰岛素后第二个获准用于治疗1型糖尿病的药物。
本品获准作为胰岛素的补充疗法用于强化的单一胰岛素治疗血糖仍不能得到满意控制的病人。但是本品的外包装上将带有“可能有低血糖风险”的警告字样。Amylin公司宣称本品将在获准90天内上市。
本品的安全性和有效性研究涉及约5000例病人，总的来说可改善血糖控制并降低体重。糖尿病人良好的血糖控制可降低长期糖尿病继发疾病的风险，这些继发病包括失明、肾病和血管病。
本品只能与胰岛素联合应用帮助降低餐后3小时内的血糖水平。出于以下三方面的原因，本品的说明书及外包装将带有风险提示及用药指导：首先，本品可能有低血糖的风险，这是1型糖尿病人和有胃轻瘫病人的最大危险；其次，可能会发生用药错误，尤其是本品与胰岛素混合于同一注射器时可改变胰岛素的活性，这点在用药指导和药品说明书中要重点强调。最后，病人有标签外使用的可能性，但这样用法潜在的益处/风险并未得到证明，标签外使用应得到有效临控。
Lehman兄弟公司的分析家认为Amylin可能藉此成为糖尿病治疗领域的领，先者。下月Amylin及其研发伙伴礼来（Eli Lilly）公司可能会获得另一糖尿病药物—exenatide的上市许可，这个药物获准后预计可达15亿美元的销售额。 而本品预计最高年销售额只有2.4亿美元左右。

【原产地英文商品名】SYMLIN 0.6MG/ML 5ML/VIAL
【原产地英文药品名】PRAMLINTIDE ACETATE
【中文参考商品译名】SYMLIN 0.6毫克/毫升 5毫升/瓶
【中文参考药品译名】醋酸普兰林肽
【生产厂家中文参考译名】Amylin Pharmaceuticals, Inc
【生产厂家英文名】Amylin Pharmaceuticals, Inc

Symlin (pramlintide)
Company: Amylin Pharmaceuticals
Approval Status: Approved March 2005
Treatment for: Diabetes
Areas: Diabetes / Endocrinology

General Information
Symlin (pramlintide) is a antihyperglycemic agent. It is designed to mimic the activity of the naturally occurring hormone amylin, which is secreted together with insulin and is involved in post-prandial glucose control.

Symlin is specifically indicated for the mealtime treatment of Type I and Type II diabetes in combination with standard insulin therapy, in patients who have failed to achieve adequate glucose control on insulin monotherapy. It can be administered to type II diabetics also on metformin or sulfonylurea therapy.

Symlin is supplied as a clear sterile solution designed for subcutaneous injection. Recommended dosing varies depending on whether a patient has Type I or Type II diabetes: for Type I patients, initial recommended dosing is 15 mcg, which should be titrated at 15 mcg increments to a maintenance dose of 30 mcg or 60 mcg as tolerated. For Type II patients, initial dose should be 60 mcg, with a single increment increase to 120 mcg as tolerated. NOTE: Initiation of Symlin therapy may require adjustments to insulin dosing schedules, and should be performed under the close supervision of a healthcare professional.

Clinical Results
FDA Approval
Approval of Symlin was supported by a number of clinical trials, investigating the drug in both Type I and Type II diabetic in both short- and long-term controlled trials, long term uncontrolled trials, and an open label study.

Type I Diabetes
Symlin was evaluated for the treatment of Type I diabetics (n=1717) in 3 long-term randomized, double-blind, placebo-controlled studies. Patients received 30 mcg or 60 mcg Symlin in addition to standard insulin therapy; in 2 of the trials, only minimal insulin dose adjustment was allowed, in order to isolate Symlin's efficacy; in the third, insulin dose was adjusted per standard medical practices. Symlin administration was seen to produce significant improvements in a number of measures at 6 months, including: change in HbA1c levels vs. baseline (-0.43%); placebo-subtracted HbA1c levels (-0.33%); change in total body weight (-1.1 kg); and placebo-subtracted total body weight (-1.7 kg).

The drug was also investigated for the treatment of Type I diabetes in a dose titration study. This randomized, double-blind, placebo-controlled study enrolled patients with relatively good glycemic control (mean HbA1c = 8.1%). In addition to maintained standard insulin regimens, subjects received an initial dose of 15 mcg Symlin or placebo, which was titrated in 15 mcg intervals to 30 mcg or 60 mcg, based on whether subjects experienced significant nausea. Insulin dosing was reduced 30-50% during titration to reduce potential incidence of hypoglycemia. At 6 months, subjects receiving Symlin plus insulin achieved similar reductions in mean HbA1C levels, compared to subjects receiving placebo-plus-insulin (-0.47 +/- 0.07 % vs. -0.49 +/- 0.07 %, respectively), while using a significantly lower total and fast-acting insulin dose (-11.7%, -22.8% from baseline). Symlin also produced weight loss relative to both baseline (-1.33) and placebo-plus-insulin (-2.6 kg)

Finally, Symlin was studied in the treatment of Type I diabetes in an open-label clinical practice setting. Using a flexible dose regimen of insulin, the study enrolled Type I diabetics unable to achieve glycemic control on insulin alone. The addition of Symlin to this regimen significantly reduced mean HbA1c levels (-0.18%) and body weight (-3.0 kg) at 6 months, and reduced total, short-acting, and long-acting insulin (-12.0 +/- 1.36, -21.7 +/- 2.81, and -0.4 +/- 1.59 %, respectively), all relative to baseline.

Type II Diabetes
Symlin was investigated for the treatment of Type II diabetes in a pair of long-term randomized, double-blind, placebo-controlled studies. Patients received Symlin or placebo, in addition to the patients existing regimens of fixed dose insulin with or without metformin and/or sulfonylurea. Symlin was found to produce significantly superior improvements in reduction in HbA1c levels (-.57 %), placebo-subtracted HbA1c levels (-0.40 %), body weight (-1.5 kg), placebo-subtracted body weight (-1.7 kg), % change in rapid-acting insulin dose (-3.0 %), and % change in long-acting insulin dose (-0.2 %), at 6 months.

Symlin was also investigated in an open-label clinical practice study in the treatment of Type II diabetics whose disease was inadequately controlled by insulin therapy. The trial enrolled 166 patients, who received 120 mcg Symlin in addition to a standard flexible-dose insulin regimen. Results indicated that the drug produced reductions from baseline in mean HbA1c levels (-0.56 +/- 0.15%) and mean body weight (-2.76 +/- 0.34 kg). Symlin administration also reduced necessary doses of total, short-acting and long-acting insulin (-6.4 +/- 2.66 %, -10.3 +/- 4.84 %, and -4.20 +/- 2.42 %, respectively).

Ongoing Study Commitments
A study of Symlin in adolescents ages 12 to less than or equal to 17 years with type 1 and type 2 diabetes to evaluate the pharmacokinetics and relevant pharmacodynamic effects of different subcutaneous doses of the drug.
Final Report Submission: September 30, 2007
A multi-center, open-label, observational study to prospectively collect data that characterize the use of Symlin following introduction into the marketplace. This study will include non-targeted prescribers in the same approximate proportion as targeted prescribers.
Protocol Submission: April 30, 2005
Study Start: September 30, 2005
Final Report Submission: September 30, 2008

Side Effects
Adverse events associated with the use of Symlin may include, but are not limited to, the following:
Nausea
Headache
Anorexia
Vomiting
Abdominal Pain
Fatigue
Dizziness
Coughing

In addition, because of Symlin's effect on the rate of gastric emptying, the drug should not be used in combination with drugs that alter gastric motility, and should not be administered simultaneously with orally-delivered drugs, as Symlin may produce changes in drug absorption rates. Further, administration of the drug without adjustment to insulin dosing levels can produce hypoglycemic events: both insulin and Symlin dosing schedules should be carefully monitored under the supervision of a healthcare professional.

Mechanism of Action
Symlin is an amlyinomimetic, a functional analog of the naturally occurring pancreatic hormone amylin. Amylin has activity in a number of gastrointestinal and glucodynamic systems, and by mimicking its activity, Symlin acts to improve glycemic control through modulation of the rate of gastric emptying, prevention of post-prandial rise in glucagon levels, and by increasing sensations of satiety, thereby reducing caloric intake and potentiating weight loss.