近日，美国食品和药物管理局（FDA）批准PrandiMet（(repaglinide and metformin HCl）片剂 ，第一种也是唯一一种固定剂量组合的速效促分泌剂格列宁（又称Prandin®）和胰岛素增敏剂二甲双胍，用于治疗2型糖尿病。
批准日期：2008年6月24日 公司：Novo Nordisk Inc.
PrandiMet（瑞格列奈和盐酸二甲双胍[repaglinide and metformin HCl]）片剂,供口服使用
美国最初批准：2008年
警告：乳酸酸中毒，查看完整的盒装警告的完整处方信息
•由于二甲双胍积聚，可能发生乳酸性酸中毒。风险增加与脓毒症，脱水，过量酒精摄入，肝损伤，肾功能损害和急性充血性心力衰竭等疾病有关。
•症状包括不适，肌痛，呼吸窘迫，增加症状和非特异性腹部窘迫。实验室异常包括低pH，增加的阴离子间隙和升高的乳酸。
•如果怀疑有酸中毒，请停止PrandiMet并立即住院。
作用机制
PrandiMet
PrandiMet结合了两种具有不同作用机制的抗高血糖药物，以改善2型糖尿病患者的血糖控制。
瑞格列奈通过刺激胰腺释放胰岛素来降低血糖水平。这个
作用取决于胰岛中功能正常的β（β）细胞。
瑞格列奈通过结合特征性位点来关闭β细胞膜中的ATP依赖性钾通道。这种钾通道阻滞使β细胞去极化，导致钙通道开放。由此导致的钙流入增加诱导胰岛素分泌。离子通道机制是高度组织选择性的，对心脏和骨骼肌的亲和力低。
二甲双胍是一种抗高血糖药物，通过降低基础和餐后血浆葡萄糖来改善2型糖尿病患者的葡萄糖耐量。二甲双胍通过增加外周葡萄糖摄取和利用来减少肝葡萄糖产生，减少肠道对葡萄糖的吸收，并改善胰岛素敏感性。使用二甲双胍治疗，胰岛素分泌保持不变，而空腹胰岛素水平和一天的血浆胰岛素反应可能实际上降低作用。
适应症和用法
•PrandiMet是一种美格列奈和双胍类药物组合产品，用于改善饮食和运动，以改善2型糖尿病患者的血糖控制，这些患者已经接受了美格列奈和二甲双胍治疗，他们对单独的美格列奈或单用二甲双胍的血糖控制不足。
重要使用限制：
•不要用于治疗1型糖尿病或糖尿病酮症酸中毒。
剂量和给药
•PrandiMet的剂量应个性化。
•从每天两次1 mg/500mg开始，除非患者已经服用更高剂量的瑞格列奈和盐酸二甲双胍
•每餐不要超过10mg瑞格列奈/2500 mg盐酸二甲双胍或每餐4mg瑞格列奈/1000mg二甲双胍。
•在饭前15分钟内分次服用。
•不吃饭的患者应该跳过PrandiMet剂量。
剂量形式和强度
片剂：
•1mg瑞格列奈/500mg盐酸二甲双胍
•2mg瑞格列奈/500mg盐酸二甲双胍
禁忌症
不要用于患者：
•肾功能不全。
•伴有代谢性酸中毒，包括糖尿病酮症酸中毒。
•接受吉非贝齐和伊曲康唑。
警告和注意事项
•二甲双胍盐酸盐在肾功能损害中是禁忌的。在启动PrandiMet之前评估肾功能，至少每年一次，并验证为正常。
•暂时停止接受碘化造影剂放射学研究的患者的PrandiMet。
•肝功能损害与乳酸性酸中毒有关。建议不要使用肝功能不全的住院患者。
•酒精可增强二甲双胍对乳酸代谢的影响。警告患者注意饮酒过量。
•PrandiMet不应与NPH胰岛素联合使用。
•Gemfibrozil大大增加瑞格列奈的暴露量。不建议联合使用葛根布齐和PrandiMet。
•瑞格列奈组分可引起低血糖。对初次接受美格列奈治疗的患者以最低可用剂量启动PrandiMet。
•二甲双胍可导致维生素B12缺乏症。每年测量一次血液学参数。
•如果在压力期间血糖控制恶化或者进食口和食物减少（例如感染，手术），可能需要停止使用PrandiMet并暂时使用胰岛素。
•没有临床研究确定使用PrandiMet或任何其他口服抗糖尿病药物降低血管风险的确凿证据。
不良反应
•低剂量血症和头痛是瑞格列奈联合二甲双胍治疗的患者中最常见的不良反应（≥10％），发生频率高于单用瑞格列奈或单用盐酸二甲双胍治疗的患者。
•胃肠道反应（例如，腹泻，恶心和呕吐）是盐酸二甲双胍治疗中最常见的不良反应，并且在更高的盐酸二甲双胍剂量下更常见。
要报告疑似不良反应，请致电1-888-NOVO-444或FDA 1-800-FDA-1088或www.fda.gov/medwatch联系Novo Nordisk。
药物相互作用
•肾小管分泌物消除的阳离子药物可能会干扰二甲双胍的消除：慎用。
•瑞格列奈部分代谢CYP2C8和CYP3A4。谨慎使用服用CYP2C8和CYP3A4抑制剂和/或诱导剂的住院患者。
包装提供/存储和处理
PrandiMet片剂以双凸面片剂形式提供，有1毫克/ 500毫克（黄色）和2毫克/ 500毫克（粉红色）强度。 平板电脑的一面是Novo Nordisk（Apis）公牛标志，另一侧是平板电脑。 将片剂着色以表明强度。
1mg/500mg（黄色） 20片剂/瓶  NDC 0169-0093-90  100片剂/瓶  NDC 0169-0093-01 
2mg/500mg（粉）   20片剂/瓶  NDC 0169-0092-90  100片剂/瓶  NDC 0169-0092-01
不要储存在25°C（77°F）以上。
防潮。 保持瓶子紧闭。
在带有安全盖的紧密容器中进行分配。
FDA Approves PrandiMet, a Replaglinide and Metformin Fixed-Dose Combination Tablet for Treatment of Type 2Diabetes
U.S. Food and Drug Administration (FDA) approved PrandiMet™ (repaglinide and metformin HCl) tablets, the first and only fixed-dose combination of the fast-acting secretagogue replaglinide (also known as Prandin®) and insulin sensitizer, metformin, for the treatment of type 2diabetes.
About PrandiMet
PrandiMet™ is indicated for the treatment of type 2 diabetes and includes two products with well-established data for safety and efficacy: repaglinide (Prandin®) and metformin. It is the first fixed-dose combination of a fast acting insulin secretagogue and metformin, combining two antihyperglycemic agents with different mechanisms of action in one tablet to improve glycemic control.
PrandiMet™ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2diabetes mellitus who are already treated with a meglitinide and metformin HCl or who have inadequate glycemic control on a meglitinide alone or metformin HCl alone. Do not use to treat type 1 diabetes or diabetic ketoacidosis.
Lactic acidosis can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure. Symptoms include malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap and elevated blood lactate.If acidosis is suspected, discontinue PrandiMet™ and hospitalize the patient immediately.
PrandiMet™ is contraindicated in patients with renal impairment, metabolic acidosis, including diabetic ketoacidosis, or patients receiving both gemfibrozil and itraconazole. Before initiation of therapy with PrandiMet™ and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal impairment is anticipated, renal function should be assessed more frequently and PrandiMet™ discontinued if evidence of renal impairment is present. PrandiMet™ should generally be avoided in patients with hepatic impairment.
PrandiMet™ should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials and may be resumed 48 hours after the procedure only after renal function has been re-eva luated and found to be normal. Repaglinide is not indicated for use in combination with NPH insulin.
Hypoglycemia and headache were the most common adverse reactions(≥10%)reported among patients treated with repaglinide in combination with metformin HCl. Gastrointestinal reactions (e.g. diarrhea, nausea, and vomiting) are the most common adverse reactions with metformin HCl treatment and are more frequent at higher metformin HCl doses.
PrandiMet™ works to control three abnormalities of type 2 diabetes: impaired insulin secretion; insulin resistance and excessive hepatic glucose production.
PrandiMet™ is available in two dosage strengths-1mg. (repaglinide)/500mg.(metformin) and 2mg.(repaglinide)/500mg.(metformin), recommended to be dosed at two-three times a day with meals.
About Type 2 Diabetes
Type 2 Diabetes (diabetes mellitus) is a serious chronic disease in which the body does not produce or properly use insulin. Insulin is a hormone needed to convert sugar, starches and other food into energy needed for daily life.
In the United States, an estimated 20.8 million people have diabetes (7% of the population). Of the total, 6.2 million remain undiagnosed and about 1.5 million new cases of diabetes are diagnosed each year.2 Only 57% of those with diabetes are meeting the recommended glucose levels (hemoglobin A1c goal of 7.0% or less)3 and those who are undiagnosed or not controlled are putting themselves at risk for serious complications.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022386lbl.pdf