Tarigan Tri Juli Edi, Dwijayanti Adisti, Setyowati Susie, Louisa Melva
Division of Endocrinology and Metabolism, Department of Internal Medicine, Dr. Cipto Mangunkusumo National Referral Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Diabetes Metab Syndr Obes. 2021 Jan 12;14:107-116. doi: 10.2147/DMSO.S279385. eCollection 2021.
To compare the immunogenicity and efficacy of insulin glargine biosimilar Ezelin (EZL) versus originator insulin glargine Lantus (LAN) as a reference basal insulin in patients with type 2 diabetes (T2D).
This was a randomized, multicenter, open-label, 24-week study in insulin-naïve patients with T2D, with HbA1c of >7.0%. We randomly assigned 133 eligible patients to receive either EZL or LAN. Baseline characteristics, including insulin autoantibody (IAA), zinc transporter 8 (ZnT8) antibody, HbA1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPPG), AST, ALT, BUN, eGFR, and oral antidiabetic drugs, were obtained before starting insulin treatment. After starting treatment, insulin dose was titrated to achieve FPG target along with oral antidiabetic drugs. Patients were given home glucometer and assisted to record plasma glucose measurement and adverse event (AE). Every month, patients came to the diabetes clinic and performed a regular physical examination and intensifying treatment if needed. Out of the 133 randomized patients, only 122 completed the study and can be examined for their IAA and ZnT8 after 6 months of treatment. The study was registered in clinicaltrials.gov, NCT03352674.
There is a similar proportion of patients with changes of IAA from baseline: 1 out of 58 (1.7%) patients receiving EZL versus 1 out of 64 (1.6%) patients receiving LAN (p = 1.000). One patient in the EZL group (1.7%) versus none in the LAN group experienced a change of ZnT8 antibody from baseline. Similar glucose control in EZL versus LAN was determined by the change in HbA1c, FPG, and 2hPPG (-2.0%, -67.46 mg/dL, and -76.51 mg/dL in the EZL group versus -1.7%, -58.11 mg/dL, and -70.03 mg/dL in the LAN group). There were six events of documented hypoglycemia in the EZL group versus five events in the LAN group. No patients experienced diabetic ketoacidosis during the study.
Overall, insulin glargine biosimilar EZL and originator insulin glargine LAN have shown a similar immunogenicity profile, as well as efficacy in providing glucose control and safety findings in T2D populations.
比较甘精胰岛素生物类似药伊泽林（EZL）与原研甘精胰岛素来得时（LAN）作为2型糖尿病（T2D）患者基础胰岛素的免疫原性和疗效。
这是一项针对初治T2D患者且糖化血红蛋白（HbA1c）>7.0%的随机、多中心、开放标签的24周研究。我们将133例符合条件的患者随机分配接受EZL或LAN治疗。在开始胰岛素治疗前获取基线特征，包括胰岛素自身抗体（IAA）、锌转运体8（ZnT8）抗体、HbA1C、空腹血糖（FPG）、餐后2小时血糖（2hPPG）、谷草转氨酶（AST）谷丙转氨酶（ALT）、血尿素氮（BUN）、估算肾小球滤过率（eGFR）及口服降糖药。开始治疗后，胰岛素剂量进行滴定以联合口服降糖药实现FPG目标。为患者提供家用血糖仪并协助记录血糖测量值和不良事件（AE）。每月患者前往糖尿病门诊进行常规体格检查并在需要时强化治疗。在133例随机分组的患者中，仅122例完成研究，且在治疗6个月后可检测其IAA和ZnT8。该研究已在clinicaltrials.gov注册，注册号为NCT03352674。
IAA自基线起发生变化的患者比例相似：接受EZL治疗的58例患者中有1例（1.7%），接受LAN治疗的64例患者中有1例（1.6%）（p = 1.000）。EZL组有1例患者（1.7%）ZnT8抗体自基线起发生变化，而LAN组无。通过HbA1c、FPG和2hPPG的变化确定EZL与LAN的血糖控制情况相似（EZL组分别为-2.0%、-67.46 mg/dL和-76.51 mg/dL，LAN组分别为-1.7%、-58.11 mg/dL和-70.03 mg/dL）。EZL组有6例记录在案的低血糖事件，LAN组有5例。研究期间无患者发生糖尿病酮症酸中毒。
总体而言，甘精胰岛素生物类似药EZL与原研甘精胰岛素LAN在T2D人群中显示出相似的免疫原性特征，以及在血糖控制和安全性方面的疗效。
