商品名：Farxiga (美国), Forxiga(欧盟)
通用名：Dapagliflozin
中文名：达格列净
别名：BMS-512148
CAS 登录号：461432-26-8
英文化学名: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl) phenyl] -6-(hydroxymethyl) tetrahydro-2H-pyran-3,4,5-triol
中文化学名：(1S)-1,5-脱水-1-C-[4-氯-3-[(4-乙氧基苯基)甲基]苯基]-D-葡萄糖醇
适应症：II型糖尿病
药物作用机制:钠－葡萄糖协同转运蛋白-2(SGLT2)抑制剂
使用方法：口服1次/1天
上市时间：2012年11月12日（欧盟,英国)，2013年1月8日（美国)
开发药企：百时美施贵宝和阿斯利康

适应证和用途
FARXIGA是一种钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂适用在有2型糖尿病成人中作为辅助饮食和运动改善血糖控制。
使用限制：不为1型糖尿病或糖尿病酮症酸中毒治疗。
剂量和给药方法
（1）推荐起始剂量是5mg每天1次，早晨服用，有或无食物。
（2）在耐受FARXIGA需要附加血糖控制患者中剂量可增加至10 mg每天1次。
（3）开始FARXIGA前评估肾功能。如eGFR低于60 mL/min/1.73 m2不要开始FARXIGA。
（4）终止FARXIGA如eGFR下降持续低于60mL/min/1.73 m2。
剂型和规格
片：5mg和10mg。
禁忌证
（1）对FARXIGA严重超敏反应史。
（2）严重肾受损，肾病终末期，或透析。
警告和注意事项
（1）低血压：开始FARXIGA前，评估血容量状态和在老年人，在有肾受损或低收缩压患者，和用利尿药患者中纠正低血容量。治疗期间监视体征和症状。(5.1，6.1)
（2）肾功能受损：治疗期间监视肾功能。
（3）低血糖：在用FARXIGA服用胰岛素或一种胰岛素促分泌素患者，考虑较低剂量胰岛素或胰岛素促分泌素以减低低血糖风险。
（4）生殖器真菌感染：如适用监视和治疗。
（5）LDL-C增高：每标准医护监视和治疗。(5.5)
（6）膀胱癌：在临床试验中观察到膀胱癌不平衡。有活动性膀胱癌患者中不应使用FARXIGA和有膀胱癌既往史患者中应谨慎使用。
（7）大血管病变结局：没有临床研究确定用FARXIGA或任何其他抗糖尿病药物减低大血管风险结论性证据。
不良反应
伴随FARXIGA最常见不良反应(5%或更高发生率)是女性生殖器真菌感染，鼻咽炎，和泌尿道感染。
在特殊人群中使用
（1）妊娠：在妊娠妇女中没有适当和对照良好研究。妊娠期间只有潜在获益胜过对胎儿潜在风险才使用。
（2）哺乳母亲：终止FARXIGA或终止哺乳.
（3）老年人：与减低血管内容量相关不良反应发生率较高。
（4）肾受损：与减低血管内容量和肾功能相关不良反应发生率较高。
Forxiga is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control as:
Monotherapy
When diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance.
Add-on combination therapy
In combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.
Forxiga Generic Name
Dapagliflozin
Type
POM

Forxiga: first in new class of diabetes treatments
The SGLT2 inhibitor dapagliflozin (Forxiga) has been licensed for the treatment of type II diabetes.
It is indicated for use in adults: as monotherapy, when diet and exercise do not provide adequate glycaemic control, and metformin is inappropriate owing to intolerance; and in combination with other glucose-lowering agents including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control
PHARMACOLOGY
Dapagliflozin inhibits sodium-glucose co-transporter 2 (SGLT2), the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By reducing renal glucose reabsorption and increasing urinary glucose excretion, dapagliflozin improves both fasting and post-prandial plasma glucose levels independent of insulin secretion. The glucuretic effect is continuous over the 24 hour dosing interval and is sustained for the duration of treatment.1
CLINICAL STUDIES
Better than placebo over 24 weeks     
A 24-week placebo-controlled study examined the effects of dapagliflozin in adults with inadequate glycaemic control (HbA1c 7–10% [53–86mmol/mol]) despite metformin treatment. Participants were randomised to receive dapagliflozin 2.5mg, 5mg or 10mg or placebo once daily, added on to metformin. Over 24 weeks, mean HbA1c declined by 0.84% (9mmol/mol) in patients receiving dapagliflozin 10mg (n=132), compared with 0.30% (3mmol/mol) in those on placebo (n=134; p<0.0001). In the subset of patients with baseline HbA1c of 9% (75mmol/mol) or greater, levels decreased by 1.32% (14mmol/mol) with dapagliflozin 10mg (n=18) versus 0.53% (6mmol/mol) with placebo (n=22).2
Events suggestive of genital infection were more common with dapagliflozin than with placebo (8–13% vs 5%) and affected both men and women. Hypoglycaemia was generally mild and occurred at comparable rates in the dapagliflozin and placebo groups (2–4% vs 3%).2
Non-inferior to glipizide
In a 52-week active-controlled non-inferiority study, dapagliflozin was compared to glipizide as add-on therapy in 814 adults with inadequate glycaemic control (HbA1c 6.6–10% [49–86mmol/mol]) on metformin. Doses were titrated up to a maximum of 10mg dapagliflozin and 20mg glipizide daily over 18 weeks. HbA1c declined by a mean of 0.52% (6mmol/mol) in both groups over 52 weeks, indicating the non-inferiority of dapagliflozin to glipizide. Patients receiving dapagliflozin lost a mean of 3.2kg body weight, whereas those given glipizide gained a mean of 1.4kg (p<0.0001). Hypoglycaemia occurred at a more than 10-fold lower rate in the dapagliflozin group than the glipizide group (3.4% vs 39.7%), but symptoms of genital and urinary tract infection were more common with dapagliflozin than glipizide (12.3% vs 2.7% and 10.8% vs 6.4%, respectively).3
Results from a 52-week extension of this study showed a sustained effect of dapagliflozin on glycaemic control at 104 weeks compared with baseline. The initial weight reduction seen with dapagliflozin was sustained and the weight gain with glipizide persisted at 104 weeks.4
Reductions in BP observed
A pre-specified pooled analysis of 12 placebo-controlled studies found that treatment with dapagliflozin 10mg daily for 24 weeks produced reductions in systolic and diastolic blood pressure of –4.4mmHg and –2.1mmHg, respectively, compared with –0.9mmHg and –0.5mmHg, respectively, with placebo.1
Monitor renal function
In patients taking dapagliflozin, monitoring of renal function is recommended before starting treatment and at least yearly thereafter; before starting concomitant treatment with agents that might reduce renal function, and periodically thereafter; and at least two to four times per year in patients with renal function approaching moderate impairment. If renal function falls below CrCl 60ml/min or eGFR 60ml/min/1.73m2, dapagliflozin should be discontinued.1