新型降糖药物--SGLT-2抑制剂/DPP-4抑制剂的复合制剂Glyxambi®获FDA批准
近期，美国FDA（食品药监局）批准一种新型降糖药物Glyxambi（一种恩格列净/利格列汀复方制剂）用于辅助治疗2型糖尿病成年患者。Medscape网站对此进行了报道。
Glyxambi是美国首次将恩格列净（SGLT2抑制剂）和利格列汀（DPP-4抑制剂）联合制成的复方药物。该药是一天一次的口服片剂，其剂型包括：10mg恩格列净/5mg利格列汀和25mg恩格列净/5mg利格列汀两种。
英国伯明翰大学内分泌学教授Tahrani博士称，“该药可能将成为2型糖尿病治疗的二线方案基本药物，适用于调整生活方式或使用二甲双胍后血糖仍未得到控制的患者，及那些对恩格列净、利格列汀无禁忌的患者。”
Tahrani博士补充道，“利格列汀是唯一不经肾脏分泌的DPP-4抑制剂，可用于伴肾衰患者，且无需调整剂量，然而恩格列净却不能用于伴慢性晚期肾衰或正在透析的患者。”
需注意的是，Glyxambi禁用于1型糖尿病患者和胰腺炎患者。
药物的作用机制、三联疗法的应用？
该结果由德克萨斯大学DeFronzo教授及其同事发表在1月12日的Diabetes Care在线杂志上。
DeFronzo 博士称：“相比恩格列净和利格列汀单独治疗， Glyxambi与二甲双胍联合治疗具有更好的降血糖疗效，同时发生低血糖的风险也明显降低。此外，Glyxambi有较好的耐受性，安全性也与恩格列净及利格列汀相似。三联疗法可用于对二甲双胍不敏感的患者，且可能具有明显益处。”
DeFronzo博士很早就提倡此种“三联疗法”，他认为相比传统疗法，三联疗法能更好地降低HbA1c，低血糖和体重增加的发生程度也明显降低。
另一项试验表明，SGLT2抑制剂和DPP-4抑制剂的互补作用可产生以上优势，而近期已发表的一项2期试验结果也显示，恩格列净/利格列汀复合物能降低罹患低血糖的风险。DeFronzo博士认为“这两种药有不同的作用机理，因此联合治疗2型糖尿病是有逻辑和理据的。”
New Drugs Online Report for empagliflozin + linagliptin
Information
Generic Name: empagliflozin + linagliptin
Trade Name: Glyxambi
Synonym: BI 10773/BI 1356
Entry Type: New formulation
Development and Regulatory status
UK: Phase III Clinical Trials
EU: Phase III Clinical Trials
US: Approved (Licensed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Feb 15: Approved in the US [7].
03/02/2015 13:23:02
Apr 14: Filed in the US for the treatment of T2DM [4]
14/04/2014 21:01:20
Aug 11: PIII study started [1].
30/08/2011 11:56:05
Trial or other data
Jan 15: Results of a 52 week phase III study (n=686) have been published in Diabetes care. At week 24, the primary end point of change from baseline in HbA1c with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin (p<0.001 for all comparisons); efficacy was maintained at week 52. The proportion of adverse events was similar across treatment arms.[6]
16/01/2015 10:09:51
Jun 14: Two 52-week PIII trials presented at the American Diabetes Association 74th Scientific Sessions. In one study (n=686) (mean baseline A1C of 8.0%), both empagliflozin/linagliptin combination doses showed statistically significant reductions in A1C vs. the empagliflozin component dose or linagliptin alone. Statistically significantly more adults who had A1C levels of 7.0% or more at baseline achieved A1C levels less than 7.0% after 24 weeks with both doses of the empagliflozin/linagliptin combination versus either empagliflozin or linagliptin alone. Empagliflozin 25 mg/linagliptin 5 mg 61.8%; empagliflozin 10 mg/linagliptin 5 mg 57.8%; empagliflozin 25 mg 32.6%; empagliflozin 10 mg 28.0%; linagliptin 5 mg 36.1%. For adults who had A1C levels of 8.5% or greater at baseline, empagliflozin 25 mg/linagliptin 5 mg combination reduced A1C by 1.8% vs. 1.2% for empagliflozin 25 mg. Epagliflozin 10 mg/linagliptin 5 mg combination reduced A1C by 1.6% vs. 1.3% for empagliflozin 10 mg. Linagliptin 5 mg alone reduced A1C by 1.0%. Empagliflozin/linagliptin combinations resulted in weight loss similar to that of empagliflozin monotherapy. Empagliflozin 25 mg/linagliptin 5 mg: body weight reduction of 3.0 kg from a mean baseline of 85.5 kg. Empagliflozin 10 mg/linagliptin 5 mg: body weight reduction of 2.6 kg from a mean baseline of 86.6 kg. Empagliflozin 25 mg: body weight reduction of 3.2 kg from a mean baseline of 87.7 kg. Empagliflozin 10 mg: body weight reduction of 2.5 kg from a mean baseline of 86.1 kg. In the second study (n=677) (mean A1C of 8.0% at baseline) A1C reduction with the empagliflozin 25 mg/linagliptin 5 mg combination was not statistically significantly greater than that of empagliflozin 25 mg. A1C reduction with the empagliflozin 10 mg/linagliptin 5 mg combination was significantly greater than that of empagliflozin 10 mg alone. Compared with linagliptin 5 mg, both combination doses significantly reduced A1C and body weight. Significantly more adults who had A1C levels of 7.0% or more at baseline achieved A1C levels less than 7.0% after 24 weeks with both doses of the empagliflozin/linagliptin combination versus the empagliflozin component dose or linagliptin alone. Empagliflozin 25 mg/linagliptin 5 mg 55.4%; empagliflozin 10 mg/linagliptin 5 mg 62.3%; empagliflozin 25 mg 41.5%; empagliflozin 10 mg 38.8%; linagliptin 5 mg 32.3% [5].
16/06/2014 16:45:50
Mar 13: PIII study started in December 2012 in patients with type-2 diabetes mellitus inadequately-controlled on once-daily linagliptin on a background of metformin (EudraCT2012-002270-31; NCT01734785). The fixed-dose combination, 10 or 25 mg empagliflozin with 5mg linagliptin once-daily, will be compared with linagliptin alone or placebo. [3]
02/04/2013 15:40:57
Aug 11: NCT01422876: a PIII randomized, double-blind, parallel group study of once daily oral of empagliflozin 25mg/ linagliptin 5mg and empagliflozin 10mg/ linagliptin 5mg fixed dose combination tablets vs the individual components for 52 weeks in 1300 treatment naïve and metformin treated patients with T2DM with insufficient glycaemic control (HbA1c between 7 to10.5%). The primary outcome is change from baseline in HbA1c at 24 weeks. The study will start Aug 11 and is due to complete Sep 13 [1].
30/08/2011 11:56:15
References
Available only to registered users
Category
BNF Category: Other antidiabetics (06.01.02.03)
Pharmacology: Fixed-dose combination of a sodium glucose co-transporter type 2 (SGLT-2) inhibitor plus dipeptidyl peptidase-4 (DPP4) inhibitor
Epidemiology: Over 5% of men & 4% of women in England have diagnosed diabetes, & it has been estimated that 3.1% of men & 1.5% of women aged 35 and over have undiagnosed diabetes (85% type 2) [2].
Indication: Type 2 diabetes mellitus
Method(s) of Administration
Oral
Company Information
Name: Boehringer Ingelheim
US Name: Boehringer Ingelheim
Further Information
Anticipated commissioning route (England) -
High cost drug list? Awaiting Update
Implications Available only to registered users |
