Medical College, Federal University of Minas Gerais (UFMG), Av. Antônio Carlos, 6627, Bloco 02, sl 1048, CEP 31270-901, Belo Horizonte, MG, Brazil,
Appl Health Econ Health Policy. 2014 Feb;12(1):19-32. doi: 10.1007/s40258-013-0073-6.
The costs of the insulin analogue (insulin glargine) have been growing appreciably in the State of Minas Gerais in Brazil, averaging 291% per year in recent years. This growth has been driven by an increasing number of successful law suits and a 536% price difference between insulin glargine and neutral protamine Hagedorn (NPH) insulin. One potential way to address this is to undertake a systematic review assessing the efficacy and safety of insulin glargine analogue compared with NPH insulin in patients with type 1 diabetes mellitus (T1DM), and, as a result, provide published data to support future recommended activities by the State of Minas Gerais. These could include maintaining it on the list of the Public Health System (SUS) provided there is a price reduction. Alternatively, the review could provide potential arguments to defend against future law suits should the authorities decide to delist insulin glargine.
A systematic review of published studies researching the effectiveness of insulin glargine in patients with T1DM between January 1970 and July 2009 in MEDLINE (PubMed), the Latin American and Caribbean Centre on Health Sciences Information, the Cochrane Controlled Trials Databases and the National Health Service Centre for Reviews and Dissemination. Inclusion criteria included insulin glargine on its own or combined with other insulin formulations. Only randomised controlled clinical trials were included. Initially, the titles of all studies were assessed by two independent reviewers before being potentially discarded, with the quality of papers assessed using a modified Jadad scale. The outcome measures included blood levels of glycated haemoglobin, episodes of hypoglycaemia, adverse effects and the reduction of microvascular and macrovascular end-organ complications of T1DM.
Out of 803 studies found in the selected databases, only eight trials met the inclusion criteria. Most of the studies were of poor methodological quality or had a high risk of bias, with a mean score of 2.125 on the Jadad scale. No study could be classified as double-blind, and only one study documented the increased efficacy of insulin glargine in relation to both glycaemic control and hypoglycaemic episodes. Typically, there was no significant difference between insulin glargine and NPH insulins.
This systematic review showed no therapeutic benefit of insulin glargine over other insulin formulations studied when analysing together glycaemic control and the frequency and severity of hypoglycaemia. We therefore recommend to the State Authority to delist insulin glargine or renegotiate a price reduction with the manufacturer. This systematic review provides support for this decision as well as documentation to combat potential law suits if discussions are unsatisfactory.
在巴西米纳斯吉拉斯州，胰岛素类似物（甘精胰岛素）的成本近年来显著增长，平均每年增长 291%。这种增长是由越来越多的成功诉讼以及甘精胰岛素和中性鱼精蛋白锌胰岛素（NPH）胰岛素之间 536%的价格差异推动的。解决这个问题的一种潜在方法是进行系统评价，评估 1 型糖尿病（T1DM）患者使用甘精胰岛素类似物与 NPH 胰岛素的疗效和安全性，从而提供已发表的数据来支持米纳斯吉拉斯州未来的推荐活动。这些活动可能包括维持甘精胰岛素在公共卫生系统（SUS）的名单上，只要价格降低。或者，如果当局决定取消甘精胰岛素的上市，该评价也可以为未来的诉讼提供潜在的辩护依据。
对 1970 年 1 月至 2009 年 7 月期间在 MEDLINE（PubMed）、拉丁美洲和加勒比卫生科学信息中心、Cochrane 对照试验数据库和国家卫生服务中心的评价与传播（National Health Service Centre for Reviews and Dissemination）中发表的关于 T1DM 患者使用甘精胰岛素有效性的研究进行系统评价。纳入标准包括甘精胰岛素单独使用或与其他胰岛素制剂联合使用。仅纳入随机对照临床试验。最初，两名独立评审员评估所有研究的标题，然后再对其进行潜在排除，使用改良 Jadad 量表评估论文的质量。观察指标包括糖化血红蛋白水平、低血糖发作、不良反应以及 T1DM 微血管和大血管终末器官并发症的减少。
在选定的数据库中，共发现 803 项研究，只有 8 项试验符合纳入标准。大多数研究的方法学质量较差或偏倚风险较高，Jadad 量表平均得分为 2.125。没有研究可归类为双盲，只有一项研究记录了甘精胰岛素在血糖控制和低血糖发作方面的疗效优于其他胰岛素制剂。通常情况下，甘精胰岛素与 NPH 胰岛素之间没有显著差异。
当综合分析血糖控制和低血糖发作的频率和严重程度时，本系统评价显示甘精胰岛素在治疗效果上并不优于其他研究的胰岛素制剂。因此，我们建议州政府取消甘精胰岛素的上市或与制造商重新谈判降价。本系统评价为这一决定提供了支持，并提供了如果谈判不满意，可用于应对潜在诉讼的文件。
