Department of Endocrinology, Diabetes, and Metabolism,University Hospital Basel, Basel, Switzerland.
Diabetes Care. 2012 Aug;35(8):1654-62. doi: 10.2337/dc11-2219. Epub 2012 Jun 14.
Metabolic activation of the innate immune system governed by interleukin (IL)-1β contributes to β-cell failure in type 2 diabetes. Gevokizumab is a novel, human-engineered monoclonal anti-IL-1β antibody. We evaluated the safety and biological activity of gevokizumab in patients with type 2 diabetes.
In a placebo-controlled, dose-escalation study, a total of 98 patients were randomly assigned to placebo (17 subjects) or gevokizumab (81 subjects) at increasing doses and dosing schedules. The primary objective of the study was to evaluate the safety profile of gevokizumab in type 2 diabetes. The secondary objectives were to assess pharmacokinetics for different dose levels, routes of administration, and regimens and to assess biological activity.
The study drug was well tolerated with no serious adverse events. There was one hypoglycemic event whereupon concomitant insulin treatment had to be reduced. Clearance of gevokizumab was consistent with that for a human IgG(2), with a half-life of 22 days. In the combined intermediate-dose group (single doses of 0.03 and 0.1 mg/kg), the mean placebo-corrected decrease in glycated hemoglobin was 0.11, 0.44, and 0.85% after 1, 2 (P = 0.017), and 3 (P = 0.049) months, respectively, along with enhanced C-peptide secretion, increased insulin sensitivity, and a reduction in C-reactive protein and spontaneous and inducible cytokines.
This novel IL-1β-neutralizing antibody improved glycemia, possibly via restored insulin production and action, and reduced inflammation in patients with type 2 diabetes. This therapeutic agent may be able to be used on a once-every-month or longer schedule.
由白细胞介素（IL）-1β调控的固有免疫系统的代谢激活导致 2 型糖尿病中的β细胞衰竭。Gevokizumab 是一种新型的人源化单克隆抗 IL-1β抗体。我们评估了 gevokizumab 在 2 型糖尿病患者中的安全性和生物学活性。
在一项安慰剂对照、剂量递增的研究中，共有 98 例患者被随机分配至安慰剂（17 例）或 gevokizumab（81 例）组，递增剂量和给药方案。该研究的主要目的是评估 gevokizumab 在 2 型糖尿病中的安全性。次要目的是评估不同剂量水平、给药途径和方案的药代动力学，并评估生物学活性。
研究药物具有良好的耐受性，无严重不良事件。有 1 例低血糖事件，随后必须减少胰岛素的同时治疗。Gevokizumab 的清除与人类 IgG（2）一致，半衰期为 22 天。在联合中间剂量组（0.03 和 0.1mg/kg 的单次剂量）中，糖化血红蛋白的平均安慰剂校正降低值分别为 1、2（P = 0.017）和 3 个月后 0.11%、0.44%和 0.85%，同时伴有 C-肽分泌增加、胰岛素敏感性增强以及 C 反应蛋白和自发性及诱导性细胞因子减少。
这种新型的 IL-1β中和抗体改善了血糖水平，可能是通过恢复胰岛素的产生和作用，以及降低 2 型糖尿病患者的炎症。这种治疗剂可能能够每 1 个月或更长时间使用一次。
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