首个钠葡萄糖共转运体2抑制剂与二肽基肽酶-4抑制剂双重机制结合的糖尿病治疗药在美国FDA批准上市
2015年2月9日,美国FDA批准新型复方降糖药物Glyxambi（恩格列净/利格列汀）上市，用于2型糖尿病成年患者的辅助治疗。
Glyxambi是一天一次的口服片剂，有10mg恩格列净/5mg利格列汀和25mg恩格列净/5mg利格列汀两种剂型。
该药也是目前美国唯一的一款SGLT2抑制剂（恩格列净[empagliflozin]，勃林格殷格翰）和DPP-4抑制剂（利格列汀 linagliptin,礼来)的复方药物。
FDA的批准基于一项3期随机临床试验，该试验纳入686例正接受高剂量二甲双胍治疗的2型糖尿病患者，评估恩格列净/利格列汀复方药物Glyxambi相比两种药物成分单独用药的疗效和安全性。
结果显示，相比恩格列净和利格列汀单独治疗，加入Glyxambi与二甲双胍联合治疗24周可显著降低HbA1c。基线HbA1c为8.0%，10mg/5mg和25mg/5mg的Glyxambi治疗分别使HbA1c降低至6.9%和6.7%。相比之下，10mg和25mg恩格列净单独治疗分别使HbA1c降低至7.3%和7.4%，5mg利格列汀使HbA1c降低至7.3%。
10mg/5mg和25mg/5mg的Glyxambi治疗组HbA1c低于7%的达标率分别为58%和62%，而10mg和25mg恩格列净、5mg利格列汀单独治疗的达标率分别为28%、33%、36%。
此外，Glyxambi相比利格列汀单独治疗可显著减轻体重。
在治疗52周时，10mg/5mg和25mg/5mg的Glyxambi治疗组低血糖发生率分别为2.2%和3.6%。试验期间无严重低血糖事件发生。
Glyxambi治疗最常见的不良反应是尿路感染、鼻咽炎和上呼吸道感染。
Glyxambi禁用于1型糖尿病患者和胰腺炎患者。

Glyxambi (empagliflozin/linagliptin)
Glyxambi Approval History
•FDA approved: Yes (First approved January 30th, 2015)
•Brand name: Glyxambi
•Generic name: empagliflozin and linagliptin
•Company: Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company
•Treatment for: Diabetes, Type 2
Glyxambi (empagliflozin and linagliptin) is a sodium glucose co-transporter-2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination for the treatment of adults with type 2 diabetes.
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) - 
In timetable: -  
PbR Awaiting Update