Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial.
Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial.
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DOI：
10.2337/dc11-0606
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发表时间：
2011-09
期刊：
影响因子：
16.2
通讯作者：
Parikh SJ
中科院分区：
文献类型：
--
作者：
Nauck MA;Del Prato S;Meier JJ;Durán-García S;Rohwedder K;Elze M;Parikh SJ
虽然磺脲类药物最初有效，但与血糖耐受性差、体重增加和低血糖有关。达格列净是一种钠-葡萄糖协同转运蛋白2（SGLT 2）的选择性抑制剂，通过增加不依赖于胰岛素的尿糖排泄来降低高血糖症，并且可能导致较少的这些不良反应。我们比较了达格列净与磺脲类格列吡嗪在二甲双胍单药治疗控制不佳的2型糖尿病患者中的疗效、安全性和耐受性。这项为期52周、双盲、多中心、活性对照、非劣效性试验将正在接受二甲双胍单药治疗的2型糖尿病患者（基线平均HbA1c，7.7%）随机分配至添加达格列净（n = 406）或格列吡嗪（n = 408），根据血糖反应和耐受性，在18周内分别上调剂量至≤ 10或≤ 20 mg/天。主要终点，与格列吡嗪（− 0.52%）相比，达格列净（− 0.52%）的HbA1c校正均值降低在52周时具有统计学非劣效性。关键次要终点：达格列净产生显著的校正平均体重减轻（− 3.2 kg）与体重增加（1.2 kg; P <0.0001）与格列吡嗪相比，显著增加了体重减轻≥ 5%的患者比例（33.3%）与格列吡嗪相比（2.5%; P <0.0001），并显著降低发生低血糖的比例（3.5%）与格列吡嗪（40.8%; P <0.0001）。与格列吡嗪相比，达格列净组更常报告提示生殖器感染和下尿路感染的事件，但对标准治疗有反应，很少导致研究中止。尽管52周的血糖疗效相似，但在二甲双胍控制不佳的2型糖尿病患者中，达格列净减轻了体重，并产生了比格列吡嗪更少的低血糖。需要进行长期研究以进一步评价SGLT 2抑制剂的生殖器和尿路感染。
Although initially effective, sulfonylureas are associated with poor glycemic durability, weight gain, and hypoglycemia. Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects. We compared the efficacy, safety, and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy. This 52-week, double-blind, multicenter, active-controlled, noninferiority trial randomized patients with type 2 diabetes (baseline mean HbA1c, 7.7%), who were receiving metformin monotherapy, to add-on dapagliflozin (n = 406) or glipizide (n = 408) up-titrated over 18 weeks, based on glycemic response and tolerability, to ≤10 or ≤20 mg/day, respectively. The primary end point, adjusted mean HbA1c reduction with dapagliflozin (−0.52%) compared with glipizide (−0.52%), was statistically noninferior at 52 weeks. Key secondary end points: dapagliflozin produced significant adjusted mean weight loss (−3.2 kg) versus weight gain (1.2 kg; P < 0.0001) with glipizide, significantly increased the proportion of patients achieving ≥5% body weight reduction (33.3%) versus glipizide (2.5%; P < 0.0001), and significantly decreased the proportion experiencing hypoglycemia (3.5%) versus glipizide (40.8%; P < 0.0001). Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to standard treatment and rarely led to study discontinuation. Despite similar 52-week glycemic efficacy, dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin. Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors.