ST LOUIS (MD Consult) - On November 5, 2010, Bristol-Myers Squibb and AstraZeneca announced that the US Food and Drug Administration (FDA) has approved Kombiglyze XR for the treatment of type 2 diabetes in adults. Kombiglyze XR is a combination of 沙克列汀 (also known as Onglyza), a dipeptidyl peptidase-4 inhibitor, with an extended-release formulation of metformin, a biguanide, in a once-daily tablet. The manufacturer states that the use of Kombiglyze XR affords strong glycemic control across glycosylated hemoglobin (HbA_1c), fasting plasma glucose (FPG), and postprandial glucose (PPG) levels.

Kombiglyze XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both 沙克列汀 and metformin is appropriate. The drug should not be used for patients with type 1 diabetes or diabetic ketoacidosis and has not been studied in combination with insulin.

The FDA approval of Kombiglyze XR was granted on the basis of findings from 2 phase 3 clinical trials and bioequivalence studies. The purpose of the clinical studies was to evaluate the efficacy and safety of 沙克列汀 and metformin (immediate-release formulation [IR]) as separate tablets compared with placebo added to metformin IR. Bioequivalence was determined in a population of healthy adult subjects comparing Kombiglyze XR with 沙克列汀 plus metformin XR as separate tablets.

One clinical trial of 24 weeks' duration involved 1,306 treatment-naive adult patients with type 2 diabetes who had shown inadequate glycemic control on diet and exercise alone. Patients receiving Kombiglyze XR (administered as Onglyza 5 mg and metformin IR as separate tablets [n = 306; baseline HbA_1c measurement, 9.4%]), experienced significant reductions in HbA_1c measurements of –2.5%, compared with –2.0% in patients treated with metformin IR plus placebo (n = 313; baseline HbA_1c measurement, 9.4%). In addition, patients receiving Kombiglyze XR experienced statistically significant reductions in FPG and PPG versus patients receiving metformin IR plus placebo. Adverse reactions occurring in ≥5% of patients treated with 沙克列汀 5 mg plus metformin IR and more commonly than in patients treated with metformin IR alone were headache (7.5% vs 5.2%) and nasopharyngitis (6.9% vs 4.0%).

Kombiglyze XR is contraindicated in patients with renal impairment, metabolic acidosis (including diabetic ketoacidosis), and hypersensitivity to metformin. Consistent with the package insert for metformin alone, the prescribing information for Kombiglyze XR contains a boxed warning for lactic acidosis, a rare, but serious metabolic complication that can occur as a result of metformin accumulation during treatment.

Kombiglyze XR should be temporarily discontinued in patients undergoing radiologic studies with iodinated contrast materials.

圣路易斯(MD Consult)——2010年11月5日，阿斯利康公司与百时美-施贵宝公司宣布，美国食品药品管理局(FDA)已批准Kombiglyze缓释剂用于治疗成人2型糖尿病。Kombiglyze缓释剂是一种含有二肽基肽酶-IV抑制剂沙克列汀(Onglyza)和双胍类药物二甲双胍缓释剂的复方制剂，使用方法为一次1片、一天1次。生产商声明，使用Kombiglyze缓释剂可在糖化血红蛋白(HbA₁c)、空腹血糖(FPG)和餐后血糖(PPG)水平方面强化血糖的控制。

 

在可以合理应用沙克列汀与二甲双胍的情况下，Kombiglyze 缓释剂可作为饮食和锻炼的一种辅助用药来改善成人2型糖尿病患者的血糖控制。该药禁用于1型糖尿病患者或糖尿病酮症酸中毒患者，目前尚未对其与胰岛素联用进行研究。

FDA批准Kombiglyze缓释剂是以3项II期临床试验以及生物等效性研究中的结果为依据的。这些临床研究旨在评估沙克列汀+二甲双胍(速释剂[IR])(单片用药)相对于安慰剂+甲福明二甲双胍IR的疗效与安全性。通过在健康成人受试者中比较Kombiglyze缓释剂与沙克列汀+二甲双胍缓释剂(单片用药)来确定生物等效性。

一项历时24周的临床试验纳入了1,306例首次接受治疗、单纯采用饮食和锻炼血糖控制不充分的成人2型糖尿病患者。接受Kombiglyze缓释剂治疗(Onglyza 5 mg+甲福明二甲双胍IR单片用药 [n=306，基线时HbA₁c=9.4%])的患者HbA₁c水平显著下降，为-2.5%，而安慰剂+二甲双胍IR治疗组(n = 313; 基线时HbA₁c =9.4%)为-2.0%。此外，Kombiglyze缓释剂治疗组患者FPG 和 PPG水平的下降相对于安慰剂+甲福明二甲双胍IR治疗组有显著的统计学意义。沙克列汀5 mg+二甲双胍IR治疗组有≥5%的患者发生了不良反应，而且与采用二甲双胍IR单药治疗的患者相比，头痛(7.5% vs 5.2%)和鼻咽炎(6.9% vs 4.0%)更常见。

 

Kombiglyze缓释剂禁用于肾功能受损、糖尿病酮症酸中毒等代谢性酸中毒和对甲福明二甲双胍过敏的患者。与二甲双胍的包装说明书一致，Kombiglyze缓释剂的处方信息也包含一则黑框警告：乳酸中毒，这是一种罕见但较严重的代谢性并发症，可由治疗期间二甲双胍的积聚而引起。

采用碘造影剂进行放射性检查的患者应暂时停用Kombiglyze缓释剂。