Johnston Rhona, Uthman Olalekan, Cummins Ewen, Clar Christine, Royle Pamela, Colquitt Jill, Tan Bee Kang, Clegg Andrew, Shantikumar Saran, Court Rachel, O'Hare J Paul, McGrane David, Holt Tim, Waugh Norman
McMDC, Harrogate, UK.
Warwick Evidence, Division of Health Sciences, University of Warwick, Coventry, UK.
Health Technol Assess. 2017 Jan;21(2):1-218. doi: 10.3310/hta21020.
Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors.
To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin.
MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions.
Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers.
We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP).
There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking.
Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK).
The National Institute for Health Research Health Technology Assessment programme.
大多数2型糖尿病患者超重，因此初始治疗旨在减轻体重并增加体力活动。即使是适度的体重减轻也能改善血糖控制。如果需要药物治疗，首选药物是二甲双胍。然而，一些人无法耐受二甲双胍，约10%的人会出现腹泻，且肾功能不全者不能使用。本综述评估了在无法使用二甲双胍时用于单药治疗的三种最新类别的药物，即钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂。
综述达格列净（Farxiga，百时美施贵宝公司，英国卢顿）、卡格列净（Invokana，杨森公司，英国海威科姆）和恩格列净（Jardiance，默克公司，德国达姆施塔特）在无法服用二甲双胍的患者中进行单药治疗的临床有效性和成本效益。
MEDLINE（1946年至2015年2月）和EMBASE（1974年至2015年2月）中持续24周或更长时间的随机对照试验。对于不良事件，使用了更广泛的研究。三家制造商提供了资料。
系统评价和经济评估。对三种SGLT2抑制剂和关键对照进行网络荟萃分析。对三家制造商提供的资料进行严格评价。
我们纳入了三项达格列净试验，卡格列净和恩格列净各两项试验。这些试验质量良好。卡格列净和达格列净试验将它们与安慰剂进行了比较，但两项恩格列净试验纳入了活性对照。所有三种药物均显示在改善血糖控制、促进体重减轻和降低血压方面有效。
没有不同“列净”类药物的直接对比试验，也没有该组患者心血管结局的长期数据。大多数试验是与安慰剂对照。试验在并非总是具有可比性的患者组中进行，例如在基线糖化血红蛋白或体重指数方面。缺乏老年患者的数据。
达格列净、卡格列净和恩格列净在改善血糖控制方面有效，还有一定降低血压和体重的额外益处。不良反应是一小部分使用者出现泌尿生殖道感染。在单药治疗中，与格列齐特或吡格列酮相比，这三种药物似乎不具有成本效益，但可能与西他列汀（Januvia，勃林格殷格翰公司，英国布拉克内尔）具有竞争力。
英国国家卫生研究院卫生技术评估项目。
