Silva Thales B C, Almeida Paulo H R F, Araújo Vania E, Acurcio Francisco de Assis, Guerra Júnior Augusto A, Godman Brian, Alvares Juliana
School of Pharmacy, Federal University of Minas Gerais (UFMG), Minas Gerais, Brazil.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, United Kingdom.
Ther Adv Endocrinol Metab. 2018 Jun 22;9(8):241-254. doi: 10.1177/2042018818781414. eCollection 2018.
Diabetes mellitus type 1 (DM1) is an autoimmune disease characterized by metabolic destruction of pancreatic cells responsible for insulin production, with treatment based on replacing insulin. Long-acting insulin analogs are indicated for patients with DM1 who exhibit important oscillations of their daily glycemia, despite its higher cost. Our study objective was to evaluate the effectiveness and safety of two long-acting insulins, insulin glargine and detemir, in treating patients with DM1.
We undertook a systematic review with meta-analysis of observational studies (cohort and registry) available in the databases and the gray literature, and a complementary search in the journal. Outcomes assessed were: glycated hemoglobin concentration; fasting plasma or capillary glucose; occurrence of episodes of severe hypoglycemia and occurrence of nocturnal hypoglycemia. The assessment of methodological quality was performed using the Newcastle score. The meta-analyses were performed on software Review Manager 5.2.
Out of 705 publications, 8 cohort studies were included. The quality of these studies was classified as high. In the meta-analysis, results regarding episodes of severe hypoglycemia ( = 0.02) and fasting glucose ( = 0.01) were in favor of detemir. The glycated hemoglobin ( = 0.49; = 89) showed high heterogeneity and no statistically significant difference between the two. The meta-analysis of total insulin dose favored glargine ( = 0.006; = 75). The rates of nocturnal hypoglycemia (NH) were evaluated only for one study and showed a significant reduction of NH after therapy with detemir, ( < 0.0001).
Although some outcomes were favorable to detemir insulin analog, it has not been possible to identify important differences of effectiveness and safety between the two analogs. These results can help in the current debate on the inclusion of long-acting analogs on the list of reimbursed medicines in Brazil, especially with the recent introduction of an insulin glargine biosimilar at a considerably lower price.
1型糖尿病（DM1）是一种自身免疫性疾病，其特征是负责胰岛素分泌的胰腺细胞发生代谢性破坏，治疗方法主要是补充胰岛素。长效胰岛素类似物适用于尽管每日血糖波动较大但仍使用DM1的患者，尽管其成本较高。我们的研究目的是评估两种长效胰岛素，甘精胰岛素和地特胰岛素，治疗DM1患者的有效性和安全性。
我们对数据库和灰色文献中可用的观察性研究（队列研究和登记研究）进行了系统评价和荟萃分析，并在期刊中进行了补充检索。评估的结果包括：糖化血红蛋白浓度；空腹血浆或毛细血管血糖；严重低血糖发作的发生率和夜间低血糖的发生率。使用纽卡斯尔评分对方法学质量进行评估。荟萃分析在Review Manager 5.2软件上进行。
在705篇出版物中，纳入了8项队列研究。这些研究的质量被归类为高。在荟萃分析中，关于严重低血糖发作（P = 0.02）和空腹血糖（P = 0.01）的结果有利于地特胰岛素。糖化血红蛋白（P = 0.49；I² = 89）显示出高度异质性，两者之间无统计学显著差异。总胰岛素剂量的荟萃分析有利于甘精胰岛素（P = 0.006；I² = 75）。仅对一项研究评估了夜间低血糖（NH）发生率，结果显示地特胰岛素治疗后NH显著降低（P < 0.0001）。
尽管某些结果对地特胰岛素类似物有利，但尚未发现两种类似物在有效性和安全性方面的重要差异。这些结果有助于当前关于将长效类似物纳入巴西报销药品清单的辩论，特别是最近以相当低价格推出甘精胰岛素生物类似药的情况。
