ENDO 2013：meta分析显示德谷胰岛素不增加反复性低血糖风险

    第95届美国内分泌学会年会（ENDO2013）于2013年6月15-18日在美国旧金山隆重举行。大会旨在为内分泌领域研究人员提供最前沿的科学知识与技术，包括基础和临床研究。本次大会参会人数达9300位，创ENDO年会历史新高，共收到摘要约2600份，ENDO2013希望与会者能从中获得有价值的教育内容和发现新的有启发性的想法以促进临床实践。
　　一项比较德谷胰岛素与甘精胰岛素的事后荟萃分析结果表明，对于接受基础-餐时胰岛素治疗的2型糖尿病患者，德谷胰岛素与甘精胰岛素相比，反复性低血糖发生率降低了27%。此外，德谷胰岛素没有增加口服降糖药治疗患者的低血糖风险。
　　诺和诺德公司Thue Johansen博士在ENDO2013上，口头报告了本次研究结果。他和同事对5项比较每日1次德谷胰岛素(N =  2,262)和甘精胰岛素治疗(n =  1,110)2型糖尿病的3a期随机意向性治疗试验进行了荟萃分析。其中4项试验比较的是德谷胰岛素和甘精胰岛素联合口服降糖药治疗，另1项研究比较的是基础-  餐时治疗方案两种胰岛素联用餐时门冬胰岛素。反复发作的低血糖(血糖<56mg/dL或更严重)定义为24小时内发生低血糖2次。
　　在基础-餐时试验中，德谷胰岛素和甘精胰岛素治疗患者分别有38%和43%发生了反复性低血糖;4项口服降糖药治疗试验中，上述比例分别为6.1%和6.6%。
　　整个荟萃分析人群(德谷胰岛素/甘精胰岛素估计比率[ERR]：0.82，P = 0.09)或口服药人群(ERR：0.92，P  =0.70)中，2个胰岛素组反复性低血糖发生率的差异无统计学意义。然而，在基础-餐时试验中，德谷胰岛素反复性低血糖发生率较甘精胰岛素降低了27%(ERR：0.73，P  = 0.04)。

　　Johansen博士表示，“尽管德谷胰岛素作用时间长而持续，且作用机制新颖，但并没有增加24小时内复发性低血糖事件发生率，这是本次研究主要阐述的问题。在基础口服治疗试验中，德谷胰岛素和甘精胰岛素的复发性低血糖事件风险非常相似;但基础-餐时试验显示德谷胰岛素的低血糖风险显著减少。”

【研究摘要】
Rate of Recurrent Confirmed Hypoglycemia with Insulin Degludec vs.  Insulin Glargine in Patients with Type 2 Diabetes

Alan J Garber*1, Marc Evans2, Lars  Bardtrum3, Thue Johansen3 and Simon Heller4

1Baylor Coll of Med Faculty Ctr, Houston, TX,  2Llandough Hospital, Cardiff, United Kingdom, 3Novo  Nordisk A/S, Søborg, Denmark, 4University of Sheffield, Sheffield,  United Kingdom
Background Insulin degludec (IDeg) is a new basal insulin  with an ultra-long and stable glucose-lowering effect (>42 hours) with low  within-patient variability.

With any long-acting insulin there is a potential concern that an extended  action profile may increase the risk of recurrent hypoglycemia, which can lead  to hypoglycemia unawareness and a reduction in the counterregulatory response to  subsequent hypoglycemia. We have previously reported data from a prospective  meta-analysis of phase 3a trials that showed IDeg to be associated with  significantly lower rates of discrete episodes of confirmed hypoglycemia (by  17%) and nocturnal confirmed hypoglycemia (by 32%) vs. insulin glargine (IGlar)  in patients with type 2 diabetes (T2D).
In this post-hoc meta-analysis of patients with T2D, we compared IDeg and  IGlar with respect to rates of recurrent confirmed hypoglycemia.

Methods The patient-level meta-analysis included all five  phase 3a, randomized, treat-to-target trials (26 or 52 week) in which once-daily  IDeg (n=2,262) and IGlar (n=1,110) have been compared in patients with T2D. All  trials were open-label. One trial (BB trial) compared IDeg with IGlar in  basal–bolus therapy with mealtime insulin aspart; all other trials compared IDeg  and IGlar in combination with oral antidiabetic therapy (BOT trials). BB and BOT  trials were analyzed independently. Recurrent confirmed hypoglycemia (PG <56  mg/dL or severe) was defined as pairs of episodes that occurred within 24 hours  of one another, and was analyzed using a negative binomial model.

Results Overall, 38% (IDeg) and 43% (IGlar) of patients  experienced recurrent hypoglycemia in the BB trial, compared with 6.1% (IDeg)  vs. 6.6% (IGlar) of patients in the four BOT trials combined.
No statistically significant difference in rates of recurrent confirmed  hypoglycemia were found between IDeg and IGlar for the overall meta-analysis  population (estimated rate ratio (ERR) IDeg/IGlar: 0.82 [0.65; 1.03], p=0.09) or  the BOT population (ERR: 0.92 [0.62; 1.38], p=0.70). For the BB trial, a  significant, 27% lower rate of recurrent confirmed hypoglycemia was found for  IDeg vs. IGlar (ERR: 0.73 [0.54; 0.99], p=0.04).

Conclusion Despite having a longer duration of action than  IGlar, IDeg is not associated with an increased risk of developing a new  confirmed hypoglycemic episode within 24 hours of a previous episode in T2D  patients treated with BOT, and was observed to have a reduced risk in patients  treated with BB therapy.