艾格列净empagliflozin 2个III期研究显著降低血糖水平和体重
2014年6月17讯 --勃林格殷格翰-礼来糖尿病联盟6月16日在2014年第74届美国糖尿病协会科学大会（ADA2014）上公布了实验性糖尿病药物艾格列净（empagliflozin） 2个III期临床试验的数据。在一项为期2年的研究中，将艾格列净（empagliflozin）或格列美脲（glimepiride）添加至二甲双胍疗法，用于2型糖尿病（T2D）成人患者的治疗，数据表明，与格列美脲相比，艾格列净（empagliflozin）使糖化血红蛋白（HA1c）实现了更大幅度的降低，体重及血压与格列美脲治疗组相当。另一项为期52周的研究，在高剂量胰岛素（有或无二甲双胍）仍无法充分控制血糖水平的T2D患者中开展，将艾格列净（empagliflozin）或安慰剂添加至每日数次胰岛素注射疗法，数据表明，与安慰剂相比，艾格列净显著降低了血糖水平和体重，同时降低了胰岛素剂量。研究中，艾格列净的安全性与既往研究一致。
艾格列净Empagliflozin属于钠-葡萄糖协同转运蛋白-2（SGLT-2）抑制剂类药物，目前正调查用于2型糖尿病成人患者的治疗。新兴的SGLT-2抑制剂类药物，已被证实能够阻断肾脏中葡萄糖的再吸收作用，将过多的葡萄糖排泄到体外，从而达到降低血糖水平的效果，而且该降糖效果不依赖于β细胞功能和胰岛素抵抗。
艾格列净Empagliflozin仍然代表着礼来同其他制药公司SGLT-2抑制剂类药物抗衡的最佳人选，如强生的卡格列净Invokana、阿斯利康和百时美施贵宝的Farxiga（达格列净dapagliflozin）。Invokana于2013年11月获FDA批准，Farxiga则在经历长期审查推迟后也最终于今年1月获FDA批准。
2014年3月，FDA因勃林格殷格翰一处生产艾格列净的工厂出现大颗粒污染事件，拒绝了勃林格-礼来糖尿病联盟艾格列净的新药申请（NDA）。2014年6月，FDA根据3月份检查总结及充分考虑勃林格提交的支持性文档，确定勃林格药物生产工厂的质量管理及合规系统具有可接受性，撤回了此前发布的警告信。
该联盟已计划再次向FDA提交艾格列净的新药申请。
英文原文：Type 2 diabetes: Investigational compound empagliflozin as an add-on therapy significantly reduced blood glucose and body weight in two newly presented phase III trials
-- In a two-year study, empagliflozin as add-on to metformin demonstrated significantly greater decreases in A1C (blood glucose), body weight and blood pressure compared with glimepiride as add-on to metformin
-- In a 52-week study of obese, inadequately controlled adults on high insulin doses, adding empagliflozin to multiple daily insulin injections significantly reduced blood glucose and body weight with lower insulin doses vs. placebo
-- Empagliflozin safety profile was consistent with previous studies
RIDGEFIELD, Conn. and INDIANAPOLIS, June 16, 2014 /PRNewswire/ -- Two phase III clinical trials studying the efficacy and safety of the investigational compound empagliflozin in type 2 diabetes (T2D) were presented today at the American Diabetes Association 74th Scientific Sessions?, Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) and Eli Lilly and Company (NYSE: LLY) announced. In a two-year study, empagliflozin demonstrated significantly greater decreases in hemoglobin A1C (a measure of average blood glucose over the past two to three months), body weight and blood pressure compared with glimepiride as add-on to metformin in adults with T2D. In a 52-week study of obese adults with T2D on high insulin doses with or without metformin, adding empagliflozin to multiple daily insulin injections significantly reduced blood glucose and body weight with lower insulin doses compared with placebo.
"Type 2 diabetes is a challenging disease to manage because blood sugar levels are often not adequately controlled with just one medication. We are encouraged by the findings that empagliflozin in combination with other therapies reduced blood glucose levels and body weight in adults with type 2 diabetes in both of these studies," said Christophe Arbet-Engels, M.D., Ph.D., vice president, metabolic clinical development and medical affairs, BIPI. "These new data add to the known clinical profile for empagliflozin and bolster its large clinical registration program."
Empagliflozin versus glimepiride as add-on to metformin for two years
A two-year study of 1,545 randomized and treated adults with T2D compared the efficacy and safety profiles of empagliflozin 25 mg with glimepiride (1-4 mg), each in combination with metformin. At 104 weeks, patients taking empagliflozin had significantly greater reductions in A1C, body weight and systolic and diastolic blood pressure from baseline compared with patients taking glimepiride:
Mean reduction in A1C levels was 0.66 percent for empagliflozin compared with 0.55 percent for glimepiride.
Mean change in body weight was a loss of 3.1 kg for empagliflozin compared with a gain of 1.3 kg for glimepiride.
Mean change in systolic blood pressure was a reduction of 3.1 mmHg for empagliflozin compared with an increase of 2.5 mmHg for glimepiride.
Mean change in diastolic blood pressure was a reduction of 1.8 mmHg for empagliflozin compared with an increase of 0.9 mmHg for glimepiride.
Significantly fewer confirmed hypoglycemic events were reported for empagliflozin compared with glimepiride (2.5 percent vs. 24.2 percent, respectively). Overall adverse event rates in the two arms were 86.4 percent and 86.3 percent for empagliflozin and glimepiride, respectively. Urinary tract infections were reported in 13.7 percent of patients in the empagliflozin arm and 13.1 percent of patients in the glimepiride arm, and genital infections were reported in 11.8 percent and 2.2 percent for empagliflozin and glimepiride, respectively.
Empagliflozin versus placebo in obese, inadequately controlled patients with T2D on multiple daily insulin injections
In a 52-week, placebo-controlled study, the safety and efficacy of empagliflozin 10 mg or 25 mg added onto multiple daily insulin injections, with or without metformin, was studied in obese adults with T2D and inadequately controlled blood glucose levels. Mean baseline A1C level for patients in this study was 8.3 percent.
After 18 weeks, empagliflozin 10 mg and 25 mg significantly reduced A1C levels by 0.94 percent and 1.02 percent from baseline, respectively, compared with 0.50 percent with placebo. After 52 weeks, empagliflozin 10 mg and 25 mg significantly reduced A1C by 1.18 percent and 1.27 percent, respectively, compared with 0.81 percent with placebo, indicating further A1C reductions in both empagliflozin groups between 18 and 52 weeks.
After 52 weeks, patients in the empagliflozin 10 mg and 25 mg arms were taking mean total daily insulin doses that were 8.8 IU/day and 11.2 IU/day lower, respectively, than the dose patients in the placebo arm were taking. More patients with baseline A1C greater than or equal to 7 percent treated with empagliflozin also achieved A1C levels below 7 percent (19.5 percent, 31 percent and 15.1 percent of patients in the empagliflozin 10 mg, 25 mg and placebo arms, respectively).
After 52 weeks, patients in each of the empagliflozin arms had an average body weight loss of 2 kg, compared with a gain of 0.4 kg for those in the placebo arm.
Hypoglycemia was reported in 51.1 percent, 57.7 percent and 58.0 percent of patients in the empagliflozin 10 mg, 25 mg and placebo arms, respectively.
About Empagliflozin
Empagliflozin is an investigational sodium glucose co-transporter-2 (SGLT2) inhibitor and is being studied for the reduction of blood glucose levels in adults with diabetes. The emerging SGLT2 inhibitor class removes excess glucose through the urine by blocking glucose re-absorption in the kidney. Empagliflozin is being studied in one of the largest clinical registration programs in its class, comprised of more than 10 multinational clinical trials and more than 13,000 adults with T2D.
About Diabetes
Approximately 24.4 million Americans and an estimated 382 million people worldwide have type 1 or type 2 diabetes. T2D is the most common type, accounting for an estimated 85 to 95 percent of all diabetes cases. Diabetes is a chronic condition that occurs when the body either does not properly produce, or use, the hormone insulin.1
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an alliance in diabetes that centers on compounds representing several of the largest diabetes treatment classes. The alliance leverages the strengths of two of the world's leading pharmaceutical companies. By joining forces, the companies demonstrate commitment in the care of patients with diabetes and stand together to focus on patient needs. Find out more about the alliance at www.boehringer-ingelheim.com or www.lilly.com.
About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates and more than 47,400 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.
In 2013, Boehringer Ingelheim achieved net sales of about $18.7 billion (14.1 billion euro). R&D expenditure in the Prescription Medicines business corresponds to 19.5% of its net sales.
For more information please visit http://www.us.boehringer-ingelheim.com.
About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us atwww.lilly.com and http://newsroom.lilly.com/social-channels.
About Lilly Diabetes
Lilly has been a global leader in diabetes care since 1923, when we introduced the world's first commercial insulin. Today we are building upon this heritage by working to meet the diverse needs of people with diabetes and those who care for them. Through research and collaboration, a broad and growing product portfolio and a continued determination to provide real solutions—from medicines to support programs and more—we strive to make life better for all those affected by diabetes around the world. For more information, visit www.lillydiabetes.com.
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