1Chorus, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, Indiana, USA
Diabetes Care. 2013 Aug;36(8):2239-46. doi: 10.2337/dc12-1835. Epub 2013 Mar 20.
Inflammation is associated with pancreatic β-cell apoptosis and reduced insulin sensitivity. Literature suggests that interleukin (IL)-1β may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to determine the efficacy, safety, and tolerability of LY2189102, a neutralizing IL-1β antibody, in T2DM patients.
Phase II, randomized, double-blind, parallel, placebo-controlled study of subcutaneous LY2189102 (0.6, 18, and 180 mg) administered weekly for 12 weeks in T2DM patients on diet and exercise, with or without approved antidiabetic medications.
LY2189102 reduced HbA1c at 12 weeks (adjusted mean differences versus placebo: -0.27, -0.38 and -0.25% for 0.6, 18 and 180 mg doses, respectively), and fasting glucose at multiple time points compared with placebo. LY2189102 also reduced postprandial glycemia, and inflammatory biomarkers, including hs-CRP and IL-6. LY2189102 was generally well tolerated.
Weekly subcutaneous LY2189102 for 12 weeks was well tolerated, modestly reduced HbA1c and fasting glucose, and demonstrated significant anti-inflammatory effects in T2DM patients. Neutralizing IL-1β holds promise as a convenient adjuvant treatment for T2DM.
炎症与胰腺 β 细胞凋亡和胰岛素敏感性降低有关。文献表明，白细胞介素 (IL)-1β 可能参与 2 型糖尿病 (T2DM) 的发病机制。本研究旨在确定中和 IL-1β 抗体 LY2189102 在 T2DM 患者中的疗效、安全性和耐受性。
在饮食和运动的基础上，T2DM 患者接受皮下 LY2189102（0.6、18 和 180mg）每周一次，为期 12 周，或联合或不联合已批准的抗糖尿病药物，进行为期 12 周的随机、双盲、平行、安慰剂对照的 II 期研究。
LY2189102 在 12 周时降低了 HbA1c（与安慰剂相比，调整后的平均差异分别为-0.27、-0.38 和-0.25%，剂量分别为 0.6、18 和 180mg），并降低了空腹血糖在多个时间点与安慰剂相比。LY2189102 还降低了餐后血糖和炎症生物标志物，包括 hs-CRP 和 IL-6。LY2189102 一般耐受性良好。
每周皮下注射 LY2189102 12 周耐受性良好，可适度降低 HbA1c 和空腹血糖，并在 T2DM 患者中显示出显著的抗炎作用。中和 IL-1β 有望成为 T2DM 的一种方便的辅助治疗方法。
