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阿斯利康糖尿病组合疗法saxagliptin/dapagliflozin III期研究获积极数据

来源:生物谷 2014-05-14 08:41

2014年5月13日讯 /生物谷BIOON/ --阿斯利康(AstraZeneca)5月13日公布了实验性组合疗法saxagliptin/dapagliflozin一项III期研究的积极数据。该项研究是一项多中心、随机、双盲、活性药物对照、24周III期试验,在服用二甲双胍仍未能充分控制血糖水平的2型糖尿病成人患者中开展,调查了saxagliptin/dapagliflozin作为一种双重附加疗法的疗效和安全性,主要终点是24周时糖化血红蛋白HbA1c从基线水平的变化。

研究数据表明,与saxagliptin+二甲双胍治疗组和dapagliflozin+二甲双胍治疗相比,saxagliptin/dapagliflozin+二甲双胍治疗组糖化血红蛋白(HbA1c)从基线水平取得了显著更大幅度的降低(-1.47% vs -0.88%和-1.20%),并有显著更多的患者实现HbA1c水平低于7%的目标(41% vs 18%和22%)。研究中,不良事件率在各组相似。

阿斯利康计划在2014年启动一项III期试验,调查dapagliflozin用于1型糖尿病的治疗。

关于saxagliptin和dapagliflozin:

saxagliptin(沙格列汀,商品名:Onglyza)属于DPP-4抑制剂,其工作原理是在葡萄糖水平升高时通过通过增强肠促胰岛素的活性,增加胰岛素的释放,并降低肝脏产生的葡萄糖的水平。

dapagliflozin(商品名:Forxiga)是一种选择性可逆性钠-葡萄糖协同转运蛋白(SGLT2)抑制剂,独立于胰岛素发挥作用,在肾脏中选择性抑制SGLT2,可帮助患者从尿液中排出多余的葡萄糖。SGLT2是一类特异性分布在肾脏近曲小管S1段的葡萄糖转运体,其生理作用是促进葡萄糖在肾小球的重吸收。目前,该药已获FDA和欧盟批准。(生物谷Bioon.com)

英文原文:AstraZeneca announces positive results from Phase III study of saxagliptin/dapagliflozin combination in patients with type 2 diabetes inadequately controlled on metformin and outlines future development plans for the oral antidiabetic franchise

Tuesday, 13 May 2014

Study showed patients inadequately controlled on metformin achieved statistically significant reduction of HbA1c with the combination of saxagliptin and dapagliflozin versus either agent alone

Overall rates of adverse events similar between the three treatment groups, and most were reported as mild or moderate in intensity. Improvements in glycaemic control achieved without increased risk of hypoglycaemia with more patients reaching goal HbA1c levels of less than 7% and were associated with body weight reduction

AstraZeneca will commence a Phase III trial for dapagliflozin in patients with Type 1 diabetes in 2014

AstraZeneca today announced results from a Phase III study evaluating the investigational combination of saxagliptin/dapagliflozin as a dual add-on therapy in adult patients with type 2 diabetes who were inadequately controlled on metformin.

Results from the combination study found that patients treated with saxagliptin/dapagliflozin plus metformin achieved significantly greater reductions in HbA1c versus either agent alone plus metformin at 24 weeks, with an adjusted mean change from baseline HbA1c of -1.47% in the saxagliptin/dapagliflozin combination group compared to -0.88% in the saxagliptin group and -1.20% in the dapagliflozin group. More patients in the saxagliptin/dapagliflozin combination group (41%) achieved goal HbA1c levels of less than 7% compared to patients in the saxagliptin (18%) and dapagliflozin (22%) groups.1

The saxagliptin/dapagliflozin combination group achieved a significantly greater adjusted mean reduction from baseline in two-hour postprandial glucose (PPG) versus the saxagliptin group, but not the dapagliflozin group. The adjusted mean reduction in fasting plasma glucose (FPG) was greater in the saxagliptin/dapagliflozin combination group (-38 mg/dL) than the saxagliptin group (-14 mg/dL), but similar to the dapagliflozin group (-32 mg/dL). In this study, overall rates of adverse events, including hypoglycaemia, were similar between the three treatment groups, and most were reported as mild or moderate in intensity.

“Diabetes is a progressive disease in which nearly half of patients do not achieve their HbA1c goals. Despite the standard sequential use of existing therapies, there is a need for new and earlier therapeutic approaches that provide more robust HbA1c lowering,” said lead investigator Julio Rosenstock, MD, director of the Dallas Diabetes and Endocrine Center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical School, Dallas, Texas. “What we’ve observed in this trial is when the two independent mechanisms of action of saxagliptin and dapagliflozin are used in combination, significant reductions in HbA1c associated with weight loss are achieved in patients not adequately treated with metformin alone, and more patients reached the HbA1c target goal without increased risk of hypoglycaemcia while maintaining a similar safety profile to the individual monotherapies.”

“The results for the combination of saxagliptin and dapagliflozin demonstrate our continued commitment to meeting the needs of patients with type 2 diabetes by working to understand how these two medicines with independent mechanisms of action may be used together to help more patients achieve their treatment goals,” said Briggs Morrison, Executive Vice President, Global Medicines Development & Chief Medical Officer, AstraZeneca.

This 24-week, Phase III, multi-center, randomised, double-blind, active-controlled, parallel-group trial was designed to evaluate the efficacy and safety of the combination of saxagliptin/dapagliflozin as dual add-on therapy in adult patients with type 2 diabetes with inadequate glycaemic control on metformin. The primary endpoint was mean change in HbA1c from baseline to week 24. Secondary endpoints included mean change from baseline in two-hour PPG during a liquid meal test, FPG, body weight at week 24 in the saxagliptin/dapagliflozin combination group versus the saxagliptin group, and the proportion of patients who achieved glycaemic response (defined as HbA1c < 7%).1

The study included 534 adult patients with type 2 diabetes (aged ≥ 18 years) with inadequate glycaemic control (HbA1c ≥ 8% and ≤ 12%) who were receiving metformin extended-release (≥ 1,500 mg per day). Patients were randomised 1:1:1 to receive the combination of saxagliptin 5 mg and dapagliflozin 10 mg added to metformin, saxagliptin and metformin added to placebo, or dapagliflozin and metformin added to placebo, for 24 weeks.1

Future Development of AstraZeneca Oral Anti-Diabetic Franchise

Type 1 diabetes patients are dependent on lifelong insulin injections which present a constant risk for hypoglycaemic events and long term weight gain. AstraZeneca will commence a Phase III trial for dapagliflozin in patients with Type 1 diabetes in 2014.

NOTES TO EDITORS

About DPP4 inhibitors and SGLT2 inhibitors

Saxagliptin (marketed as Onglyza®) belongs to the class of medicines called DPP-4 inhibitors, which work by increasing the activity of the incretin hormones, increasing the release of insulin when glucose levels are elevated and reducing the levels of sugar produced by the liver (glucagon).2 Dapagliflozin (marketed as Farxiga™ in the U.S. and Forxiga® outside the U.S.) is part of a newer class of medicines called sodium-glucose cotransporter 2 (SGLT2) inhibitors, which remove glucose via the kidneys.

About Type 2 Diabetes

Diabetes is estimated to affect 25.8 million people in the U.S. and more than 382 million people worldwide. The prevalence of diabetes is projected to reach more than 592 million people worldwide by 20353. Type 2 diabetes accounts for approximately 90-95 percent of all cases of diagnosed diabetes in adults4. Type 2 diabetes is a chronic disease5 characterised by pathophysiologic defects leading to elevated glucose levels6. Over time, this sustained hyperglycaemia contributes to further progression of the disease7. Significant unmet needs still exist, as many patients remain inadequately controlled on their current glucose-lowering regimen.

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