美国默克制药公司每日用药一次的糖尿病治疗新药Januvia (sitagliptin)昨日通过欧洲批准。该药是第一种通过欧洲批准的二肽酰肽酶4(DPP-4)抑制剂类糖尿病复方治疗药。

Januvia用于治疗2型糖尿病，它通过提高人体降糖素系统的机能而降低血糖水平。当人体血糖水平升高时，降糖素通过两种方式控制血糖水平：其一是促使胰腺释放胰岛素；其二是向肝脏发送信号以降低葡萄糖的生成。DPP-4抑制剂可以通过增加人体降糖素的活性而帮助2型糖尿病患者控制血糖水平特别值得指出的是，当单独使用Januvia效果不理想时，该药可与metformin联用，再结合饮食和运动而达到更好的疗效。同时，它还获准与thiazolidinedione联用。

About JANUVIA

JANUVIA is a once-daily pill that, along with diet and exercise, helps lower blood sugar levels in people with type 2 diabetes. It's a type of prescription diabetes medicine called a DPP-4 inhibitor (blocker). DPP-4 blockers enhance the body's own ability to control blood sugar levels.

A doctor may prescribe JANUVIA alone or together with certain other diabetes medicines to help control blood sugar.

JANUVIA (jah-NEW-vee-ah) is a once-daily prescription pill that, along with diet and exercise, helps lower blood sugar levels in people with type 2 diabetes.

Important Information About JANUVIA

JANUVIA has not been studied with insulin and should not be used to treat patients with type 1 diabetes or diabetic ketoacidosis (increased ketones in the blood or urine) or used if you are allergic to JANUVIA. Your doctor may perform blood tests from time to time to measure how well your kidneys are working. If you have kidney problems, your doctor may prescribe lower doses of JANUVIA.

When JANUVIA is used with a sulfonylurea, low blood sugar (hypoglycemia) can occur. To avoid this risk, your doctor may prescribe lower doses of the sulfonylurea.

Allergic reactions, which may be serious, including rash, hives, and swelling of the face, lips, tongue, and throat that may cause difficulty breathing or swallowing, can occur. If you have an allergic reaction, stop taking JANUVIA and call your doctor right away. The most common side effects include upper respiratory tract infection, stuffy or runny nose and sore throat, and headache.

Information on Januvia

Learn more about usage, cautions, and possible side effects .

Bottle
Chemical Name: SITAGLIPTIN (si-ta-GLIP-tin)

Common uses
This medicine is a dipeptidyl peptidase-4 (DPP-4) inhibitor used to treat type 2 diabetes in patients who cannot control blood sugar levels by diet and exercise. It is used along with diet and exercise. This medicine may be taken alone or in combination with certain other antidiabetic medicines.

Before using
INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking. ADDITIONAL MONITORING OF YOUR DOSE OR CONDITION may be needed if you are taking digoxin. DO NOT START OR STOP any medicine without doctor or pharmacist approval. Inform your doctor of any other medical conditions including kidney problems, allergies, pregnancy, or breast-feeding. USE OF THIS MEDICINE IS NOT RECOMMENDED if you have type 1 diabetes or high blood ketone levels (diabetic ketoacidosis). Contact your doctor or pharmacist if you have any questions or concerns about taking this medicine.

Directions
Follow the directions for using this medicine provided by your doctor. An additional patient information leaflet is available with this medicine. Read it carefully. Ask your doctor, nurse, or pharmacist any questions that you may have about this medicine. This medicine may be taken on an empty stomach or with food. STORE THIS MEDICINE at room temperature between 68 and 77 degrees F (20 and 25 degrees C) away from heat, moisture, and light. Brief storage between 59 and 86 degrees F (15 and 30 degrees C) is permitted. CONTINUE TO TAKE THIS MEDICINE even if you feel well. Do not miss any doses. IF YOU MISS A DOSE OF THIS MEDICINE, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. DO NOT take 2 doses at once.

Cautions
DO NOT TAKE THIS MEDICINE if you have had an allergic reaction to it or are allergic to any ingredient in this product. Laboratory and/or medical tests, including blood glucose, hemoglobin A1C, and kidney function, may be performed to monitor your progress or to check for side effects. KEEP ALL DOCTOR AND LABORATORY APPOINTMENTS while you are taking this medicine. It may be harder for you to control your blood sugar during times of stress such as fever, infection, injury, or surgery. Talk with your doctor about how to control your blood sugar if any of these occur. Do not change the dose of your medicine without checking with your doctor. BEFORE YOU BEGIN TAKING ANY NEW MEDICINE, either prescription or over-the-counter, check with your doctor or pharmacist. CAUTION IS ADVISED WHEN USING THIS MEDICINE IN THE ELDERLY because they may be more sensitive to the effects of the medicine. FOR WOMEN: IF YOU PLAN ON BECOMING PREGNANT, discuss with your doctor the benefits and risks of using this medicine during pregnancy. IT IS UNKNOWN IF THIS MEDICINE IS EXCRETED in breast milk. IF YOU ARE OR WILL BE BREAST-FEEDING while you are using this medicine, check with your doctor or pharmacist to discuss the risks to your baby. CHECK BLOOD SUGAR LEVELS closely and ask your doctor before adjusting the dose of your diabetes medicine. MONITOR BLOOD GLUCOSE on a regular basis, as directed by your doctor.

Possible side effects
SIDE EFFECTS that may occur while taking this medicine include headache, nausea, nasal congestion, runny nose, sore throat, or upper respiratory infection. If they continue or are bothersome, check with your doctor. An allergic reaction to this medicine is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include rash, itching, swelling, dizziness, or trouble breathing. If you notice other effects not listed above, contact your doctor, nurse, or pharmacist.

Drug interactions
Drug interactions can result in unwanted side effects or prevent a medicine from doing its job. Use our drug interaction checker to find out if your medicines interact with each other. Check drug interactions

If you take too much
IF OVERDOSE IS SUSPECTED, contact your local poison control center or emergency room immediately.

Additional information
If your symptoms do not improve or if they become worse, check with your doctor. FOLLOW THE DIETARY PLAN provided by your doctor. Carry an identification card at all times that says you are diabetic. Monitor your blood sugar levels regularly according to your doctor's directions. If your blood sugar level is often higher or lower than it should be and you are taking this medicine according to directions, check with your doctor. DO NOT SHARE THIS MEDICINE with others for whom it was not prescribed. DO NOT USE THIS MEDICINE for other health conditions. KEEP THIS MEDICINE out of the reach of children.

 
美国核准JANUVIA(TM)，日服一次用于治疗2型糖尿病

美国食品药品管理局核准JANUVIA(TM)，日服一次用于治疗2型糖尿病；该药是美国市场迄今为止仅有的用于治疗2型糖尿病的二肽基肽酶-4抑制剂类药物。

美国以外称默沙东公司）今天宣布，美国食品药品管理局（FDA）已批准JANUVIA(TM)（磷酸西他列汀，sitagliptin phosphate），该药成为美国市场迄今为止仅有的用于治疗2型糖尿病的二肽基肽酶-4（DPP-4）抑制剂类药物。根据审批结果，JANUVIA可用作单一治疗药物，也可用作其它两种口服降糖药（二甲双胍或噻唑烷二酮）的辅助药物，当2型糖尿病患者节食或锻炼不足时，该药能够更好地控制患者体内的血糖（葡萄糖）水平。JANUVIA推荐剂量为，每日服用一次，每次100毫克。JANUVIA不适合1型糖尿病患者服用，也不可用于治疗糖尿病酮症酸中毒，该药对这两种疾病无效。

JANUVIA可增强自然肌体系统，从而显著降低血糖

JANUVIA属于创新型处方药物——二肽基肽酶-4（DPP-4）抑制剂的一种，能够更好地控制2型糖尿病患者体内血糖水平。JANUVIA能够增强一种称为肠降血糖素系统的自然肌体系统，该系统能够影响胰腺的β细胞和α细胞，有助于调节葡萄糖。因β细胞功能紊乱造成胰岛素减少，引起血糖升高；或因α细胞和β细胞功能紊乱造成肝脏葡萄糖合成失控，进而引发血糖升高——这时JANUVIA才会通过二肽基肽酶-4抑制剂产生药效。

波士顿哈佛医学院加斯林糖尿病中心临床研究主任、医学教授、医学博士Edward S. Horton说，“对于那些无法通过生活方式的改变，如健康饮食或加强锻炼，来有效控制疾病的2型糖尿病患者，或者需要药物来控制疾病的患者，这个新产品能够帮助他们调节血糖水平。”

默克公司总裁兼首席执行官Richard T. Clark说，“JANUVIA显示了默克公司对糖尿病领域的投入，显示了我们为那些积极治疗2型糖尿病的患者和医生所带来的益处。JANUVIA获得批准，这清楚地说明，默克公司致力于开发创新疗法，要让人人都更健康。”

JANUVIA副作用总体发生率与安慰剂水平相当

临床试验显示，JANUVIA副作用总体发生率与安慰剂的水平相当。根据临床报告，JANUVIA最常见的副作用（大于等于5％，高于安慰剂）为鼻塞、流涕、喉痛、上呼吸道感染和头痛。

JANUVIA用于单药治疗可大幅降低糖化血红蛋白（HbA1c）（1）

在两项安慰剂控制的双盲（受试者和研究者事先均不知情）研究中，实验开始时，患者糖化血红蛋白（HbA1c）水平略高或较高（平均水平为8％；受试者HbA1c水平位于7％到10％之间），一组参加24周的研究（样本数n=473），一组参加18周的研究（样本数n=296）；与使用安慰剂相比，日服JANUVIA 100毫克（每日一次），患者糖化血红蛋白水平的均数差非常明显，分别为-0.8％和-0.6％（显著性水平p小于0.001）。和治疗2型糖尿病的药剂试验的典型情况一样，在JANUVIA的作用下，糖化血红蛋白降低，其平均幅度看起来和患者的糖化血红蛋白基准水平有关。对两项单药治疗研究进行汇总分析，从预先设定的小组的情况可以看出，当患者根据初始糖化血红蛋白水平划分为略高的糖化血红蛋白水平（小于8％，样本数n=411），较高的糖化血红蛋白水平（大于或等于8％小于9％，样本数n=239）和最高的糖化血红蛋白水平（大于或等于9％，样本数n=119）三类时，与使用安慰剂相比，18周后，各组的糖化血红蛋白均数差分别为-0.6％，-0.7％和-1.4％（治疗过程中，小组相互影响的显著性水平p小于0.001）。

JANUVIA与二甲双胍或噻唑烷二酮共同服用时疗效显著，能够产生互补效应

三种关键的缺陷能够导致葡萄糖失控：因β细胞功能紊乱导致胰岛素分泌减少，因α细胞和β细胞功能紊乱导致肝脏合成葡萄糖的功能失控——JANUVIA能够应对其中两种缺陷。当胰岛素致敏物质——二甲双胍或吡格列酮（pioglitazone，噻唑烷二酮的一种）中加入JANUVIA时，胰岛素抵抗、beta细胞功能紊乱（胰岛素分泌减少）和α细胞功能紊乱（肝脏无限制合成葡萄糖）这三种2型糖尿病的关键缺陷就能解决了。

一些2型糖尿病患者如果只服用二甲双胍或吡格列酮一时无法控制病情，我们对这些患者进行了为期24周的单独研究，结果发现，每天服用一次JANUVIA（每次100毫克）能够产生互补效应。与安慰剂相比，使用JANUVIA，糖化血红蛋白水平的均数差非常显著：在二甲双胍辅助治疗研究和吡格列酮辅助治疗研究中均为-0.7％（显著性水平p均小于0.001）。在上述两项辅助研究中，使用JANUVIA之后，糖化血红蛋白水平的平均数从8.0％（二甲双胍）和8.1％（吡格列酮）的基准平均水平分别降低了0.7％和0.9％。

使用JANUVIA之后，约有两倍以上患者达到了目标，他们的糖化血红蛋白水平降低到7％以下

在二甲双胍辅助治疗研究中，使用二甲双胍不能控制病情的患者，同时服用JANUVIA时，糖化血红蛋白水平降低到7％以下的人数比例比只使用二甲双胍达到目标的患者超出两倍以上（使用JANUVIA和二甲双胍达到目标的比例占47％，而一直使用二甲双胍达到目标的比例占18％）（显著性水平p小于0.001）。与之相同，在吡格列酮辅助治疗研究中，同时服用JANUVIA达到目标，糖化血红蛋白降低到7％以下的比例为45％，而只服用吡格列酮达到目标的比例为23％（显著性水平p小于0.001）。

JANUVIA全天都能产生药效，可同时降低餐后2小时血糖（PPG）和空腹血糖（FPG），从而有效降低糖化血红蛋白水平

JANUVIA能在用餐时间、各餐间隔、整夜对葡萄糖做出全天候响应。借助安慰剂做比较，对仅服用二甲双胍一种药物不能见效的患者进行为期24周的研究，结果发现，每天另外服用100毫克JANUVIA（日服一次）能够产生显著效果，与只服用二甲双胍的患者相比，餐后2小时血糖（或称饭后血糖）每分升降低51毫克，而空腹血糖每分升降低25毫克（显著性水平p小于0.001）。

使用JANUVIA进行治疗不会增加体重，也不会带来低血糖的风险

临床试验表明，与使用安慰剂相比，日服一次JANUVIA，体重变化不大。在两项为期24周的实验中，一组患者服用JANUVIA进行单药治疗（样本数n=193），另一组患者同时服用JANUVIA和二甲双胍（样本数n=399），结果显示，患者平均体重分别下降0.2千克（使用安慰剂则下降1.1千克）和0.7千克（使用安慰剂则下降0.6千克）。整个临床研究过程中，因每日服用100毫克JANUVIA导致出现低血糖的比例与使用安慰剂时类似（分别为1.2％和0.9％）。服用JANUVIA之后，患者发生部分胃肠不良反应的情况如下：腹痛（JANUVIA：2.3％；安慰剂：2.1％），呕吐（1.4％；0.6％）和腹泻（3.0％；2.3％）。

与葡萄糖相关的作用机制

JANUVIA的创新机制在于和葡萄糖的关联作用，JANUVIA能够响应葡萄糖的增加，只在必要的时候让胰岛素释放出来，降低葡萄糖水平，这样就能降低低血糖的风险。JANUVIA通过抑制DPP-4酶，能够大幅提高肠降血糖素活性激素水平，这样，肝脏β细胞合成、释放的胰岛素就会增加，而肝脏α细胞释放的胰高血糖素则减少。

JANUVIA的适应症和禁忌症

JANUVIA可作为节食和锻炼之外的辅助治疗，用于增强2型糖尿病患者的血糖控制能力。如果2型糖尿病患者在节食和锻炼的同时，仅服用一种药剂无法有效控制血糖，这个时候，JANUVIA可与二甲双胍或噻唑烷二酮类药物同时服用。JANUVIA不适合1型糖尿病患者服用，也不可用于治疗糖尿病酮症酸中毒，JANUVIA对这些病症无效。JANUVIA没有禁忌症。

JANUVIA部分警示信息

由于JANUVIA经过肾脏排出体外，为了使用JANUVIA时达到与肾脏功能正常的患者类似的血浆浓度，建议患有轻度肾脏功能不全病症的患者，以及患有重度肾脏功能不全病症或晚期肾病（ESRD）、需要血液透析或腹膜透析的患者调整JANUVIA服用剂量。儿童患者服用JANUVIA的安全性和药效还不清楚。针对孕妇进行的安全可靠的研究项目数量不足。只有确实需要时，JANUVIA才可在妊娠期服用。向哺乳期女性开JANUVIA药时应谨慎。

JANUVIA服用剂量

建议每天服用一次JANUVIA，每次100毫克，空腹与否均可，能用于各类获得批准的适应症。患有轻度或中度肝功能不全，或患有轻度肾功能不全（肌酐清除率水平大于或等于50 mL/min）的2型糖尿病患者无需调整剂量。为了使用JANUVIA时达到与肾脏功能正常的患者类似的血浆浓度，建议患有中度或重度肾功能不全病症的患者，以及需要血液透析的肾病晚期患者减少JANUVIA服用剂量。患有中度肾功能不全病症的患者（肌酐清除率水平大于或等于30 mL/min，小于50 mL/min），JANUVIA每日服用剂量为50毫克。患有重度肾功能不全病症的患者（肌酐清除率小于30 mL/min）或需要血液透析的肾病晚期患者，JANUVIA每日服用剂量为25毫克。由于需要根据肾脏功能调整服用剂量，建议初次服用JANUVIA之前检查一下肾脏功能，开始服药后也应定期检查。