一类被称为DPP-4抑制剂的新型口服降糖药正在快速增长的糖尿病用药，成为一种高血糖症的标准疗法。    最近在美国糖尿病协会举办的科技年会中，默沙东公司、阿斯利康公司以及百时美施贵宝公司纷纷发表了它们的研究结果，这些结果显示DPP-4抑制剂与传统的降糖药二甲双胍联合使用能得到比二甲双胍单独使用更好的临床效果。对于默沙东而言，这项研究结果颇具实际意义。目前，全球第一个也是惟一一个上市的DPP-4抑制剂Januvia正是出自默沙东的科研人员之手。Januvia于去年10月正式在美国上市。今年4月，Januvia与二甲双胍的复方制剂（商品名Janumet）在美国获得上市批准。默沙东在这个重要的糖尿病学术交流会上正逢其时地发表了相关研究报道。与此同时，百时美施贵宝与阿斯利康联合开发的DPP-4抑制剂saxagliptin也已经到了最后的冲刺阶段。为此，这两大公司也需要足够的临床数据来为今后这个产品的市场命运打下坚实的基础，毕竟有利的临床研究结果不仅能推动美国FDA与其他国家的药政机构尽早为这个产品的上市打开绿灯，也能让此类新产品获得临床医师的欢心而更具市场竞争力。默沙东的研究结果主要是基于一项762名病人参加的历时54周的临床研究之上的。最终，服用Januvia/二甲双胍的病人的糖化血红蛋白（HbA1c）值比单独服用二甲双胍的病人有着明显的统计学意义上的改进。同样的，百时美施贵宝与阿斯利康联合进行的对743名病人的24周研究也发现，它们的在研产品与二甲双胍同时使用比单服二甲双胍也存在着显著的统计学差异。   由此，默沙东负责研发的一名高级经理人已经表示，单独一个药物对糖尿病的初期治疗往往是不够的，很多病人需要更全面的联合用药方案。的确，DPP-4抑制剂与过去的传统降糖药相比自有它独到的优势，它能通过双重机制来获得降低血糖的作用，在抑制了肝糖原产生葡萄糖总量的同时它还能促进胰腺分泌更多的胰岛素。从这一点上来说，DPP-4抑制剂依然定位于2型糖尿病的治疗，因为此类糖尿病人的最大问题就是无法分泌足够的胰岛素来分解体内血糖。然而，目前Januvia还不是2型糖尿病治疗的一线用药，此外，FDA将其复方制剂也定位于Januvia与二甲双胍都无法控制血糖的病人之上。为此，默沙东公司已经向FDA递交了新的临床数据，并提出将Januvia/二甲双胍复方制剂转为一线用药的申请。   JANUMET 50mg/1000mg Manufacturer Merck & Co., Inc. Legal Classification Rx Pharmacological Class Dipeptidyl peptidase-4 inhibitor + biguanide. Generic Name Sitagliptin 50mg, metformin (as HCl) 1000mg; tabs. Also • JANUMET 50mg/500mg Indications Adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are not adequately controlled on metformin or sitagliptin alone or in patients already being treated with the combination of sitagliptin and metformin. Children<18yrs: not recommended. Adults Individualize. Take twice daily with meals. Previously on metformin alone: initially 50mg twice daily of sitagliptin plus metformin dose. Previously on metformin 850mg twice daily: start with 50mg/1000mg twice daily. Previously on sitagliptin alone: initially 50mg/500mg twice daily; may increase to 50mg/1000mg twice daily. Previously on sitagliptin and metformin: switch on a mg/mg basis. Max 100mg sitagliptin/2000mg metformin per day. Contraindications Renal disease or dysfunction. Metabolic acidosis, ketoacidosis. Concomitant intravascular iodinated contrast agents (suspend during and for 48 hours after use). Type 1 diabetes. Precautions Confirm normal renal function before starting and monitor (esp. in elderly). Avoid if clinical or lab evidence of hepatic disease. Discontinue if lactic acidosis, ketoacidosis, renal impairment, shock, acute MI, acute CHF, sepsis, or hypoxemia occurs. May need to suspend therapy during periods of stress or if dehydration occurs or before surgery. Monitor hematology (esp. serum Vit. B12 in susceptible patients). Elderly, debilitated, malnourished, deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. Pregnancy (Cat.B). Nursing mothers. Interactions Cationic drugs eliminated by renal tubular secretion (eg, amiloride, digoxin, morphine, procainamide, quinine, quinidine, ranitidine, triamterene, trimethoprim, vancomycin), furosemide, nifedipine, cimetidine: may increase metformin levels. Avoid excessive alcohol intake (potentiates effects of metformin on lactate). Monitor digoxin. Diuretics, steroids, estrogens, oral contraceptives, phenothiazines, phenytoin, thyroid products, nicotinic acid, sympathomimetics, calcium channel blockers, isoniazid, others that may cause hyperglycemia. β-blockers may mask hypoglycemia. Adverse Reactions Nasopharyngitis, GI disturbances, asthenia, headache; lactic acidosis (rare, half of the cases are fatal). How Supplied Tabs—60, 180, 1000 Additional Resources • Related Prescribing Note 1:  JANUMET TAB 50/500MG UD 50 (SITAGLIPTIN PHOS/METFORMIN HCL)                             2:  JANUMET TAB 50/1000MG 60 (SITAGLIPTIN PHOS/METFORMIN HCL)