Saxagliptin Added to a Thiazolidinedione Improves Glycemic Control in Patients with Type 2 Diabetes and Inadequate Control on Thiazolidinedione Alone
Saxagliptin Added to a Thiazolidinedione Improves Glycemic Control in Patients with Type 2 Diabetes and Inadequate Control on Thiazolidinedione Alone
复制标题
DOI：
10.1210/jc.2009-0550
复制
发表时间：
2009-12-01
影响因子：
5.8
通讯作者：
Chen, Roland
中科院分区：
文献类型：
--
作者：
Hollander, Priscilla;Li, Jia;Chen, Roland
背景：由于2型糖尿病（T2D）的自然进展，大多数患者需要联合治疗来维持血糖控制。目的：评价沙格列汀联合噻唑烷二酮（TZD）治疗血糖控制不佳的t2dm患者的疗效和安全性。设计：该研究是一项多中心、随机、双盲、安慰剂（PBO）对照的3期试验，于2006年3月13日至2007年10月15日进行。环境：患者从172个门诊中心招募。患者：筛查前接受稳定TZD单药治疗（吡格列酮30或45 mg或罗格列酮4或8 mg）至少12周，T2D[糖化血红蛋白（HbA(1c)） 7.0-10.5%控制不充分的患者，年龄18-77岁。干预措施：共有565名患者随机接受沙格列汀（2.5或5mg）或PBO治疗，每日一次，加上稳定的TZD剂量，持续24周。主要结局指标：主要结局指标是HbA（1c）从基线到第24周的变化。次要结局是从基线到第24周空腹血糖的变化，达到HbA（1c）低于7.0%的患者比例，以及餐后曲线下的葡萄糖面积。结果：在24周时，沙格列汀（2.5 mg和5 mg）加TZD在HbA（1c）和空腹血糖(-0.8 mmol/l （P = 0.0053）和-1 mmol/l （P = 0.0005）与PBO的调整后平均降低具有统计学意义[-0.66% （P = 0.0007）和-0.94% (P < 0.0001) vs. -0.30%]和空腹血糖[-0.8 mmol/l （P = 0.0053）和-1 mmol/l (P = 0.0005) vs. -0.2 mmol/l]。沙格列汀（2.5 mg和5 mg）加TZD组HbA（1c）低于7.0%的患者比例高于PBO组[42.2% （P = 0.001）和41.8% （P = 0.0013）比25.6%]。餐后曲线下葡萄糖面积明显减少[-436 mmol]。min/l（沙格列汀2.5 mg + TZD）和-514 mmol。min/l（沙格列汀5mg加TZD） vs -149 mmol。最小/升(PBO)]。沙格列汀总体耐受良好；所有组的不良事件发生率和报告的低血糖事件相似。结论：与TZD单药治疗相比，沙格列汀联合TZD在血糖控制的关键参数方面具有统计学意义的改善，并且通常耐受性良好。[J] .中华内分泌杂志，2009,31(4):389 - 389。
Context: Due to the natural progression of type 2 diabetes (T2D), most patients require combination therapy to maintain glycemic control.Objective: Our objective was to evaluate efficacy and safety of saxagliptin plus thiazolidinedione (TZD) in patients with T2D and inadequate glycemic control on TZD monotherapy.Design: The study was a multicenter, randomized, double-blind, placebo (PBO)-controlled phase 3 trial conducted from March 13, 2006, to October 15, 2007.Setting: Patients were recruited from 172 outpatient centers.Patients: Patients with inadequately controlled T2D [glycosylated hemoglobin (HbA(1c)) 7.0-10.5%], 18-77 yr, receiving stable TZD monotherapy (pioglitazone 30 or 45 mg or rosiglitazone 4 or 8 mg) for at least 12 wk before screening were eligible.Interventions: A total of 565 patients were randomized and treated with saxagliptin (2.5 or 5 mg) or PBO, once daily, plus stable TZD dose for 24 wk.Main Outcome Measures: Primary outcome was change in HbA(1c) from baseline to wk 24. Secondary outcomes were change from baseline to wk 24 in fasting plasma glucose, proportion of patients achieving HbA(1c) less than 7.0%, and postprandial glucose area under the curve.Results: At 24 wk, saxagliptin (2.5 and 5 mg) plus TZD demonstrated statistically significant adjusted mean decreases vs. PBO in HbA(1c) [-0.66% (P = 0.0007) and -0.94% (P < 0.0001) vs. -0.30%] and fasting plasma glucose [-0.8 mmol/liter (P = 0.0053) and -1 mmol/liter (P = 0.0005) vs. -0.2 mmol/liter]. Proportion of patients achieving HbA(1c) less than 7.0% was greater for saxagliptin (2.5 and 5 mg) plus TZD vs. PBO [42.2% (P = 0.001) and 41.8% (P = 0.0013) vs. 25.6%]. Postprandial glucose area under the curve was significantly reduced [-436 mmol . min/liter (saxagliptin 2.5 mg plus TZD) and -514 mmol . min/liter (saxagliptin 5 mg plus TZD) vs. -149 mmol . min/liter (PBO)]. Saxagliptin was generally well tolerated; adverse event occurrence and reported hypoglycemic events were similar across all groups.Conclusions: Saxagliptin added to TZD provided statistically significant improvements in key parameters of glycemic control vs. TZD monotherapy and was generally well tolerated. (J Clin Endocrinol Metab 94: 4810-4819, 2009)