Thrasher James, Surks Howard, Nowotny Irene, Pierre Suzanne, Rotthaeuser Baerbel, Wernicke-Panten Karin, Garg Satish
1 Medical Investigations, Inc, Little Rock, AR, USA.
2 Sanofi, Bridgewater, NJ, USA.
J Diabetes Sci Technol. 2018 May;12(3):680-686. doi: 10.1177/1932296817753644. Epub 2018 Jan 23.
SAR342434 (U100; SAR-Lis; insulin lispro) is a biosimilar/follow-on to insulin lispro (U100; Ly-Lis). Similar pharmacokinetics/pharmacodynamics between the two products has been demonstrated in a hyperinsulinemic euglycemic clamp study. The current study evaluated the safety of SAR-Lis and Ly-Lis when administered by continuous subcutaneous insulin infusion (CSII; insulin pumps).
This was a randomized, open-label, 2 × 4-week, two-arm crossover study in 27 patients with type 1 diabetes mellitus (NCT02603510). The main outcome was the incidence of infusion set occlusions (ISOs), defined as failure to correct hyperglycemia (plasma glucose ≥≥ 300 mg/dl) by 50 mg/dl within 60 minutes by insulin bolus via the pump. Secondary outcomes included intervals between infusion set changes, treatment-emergent adverse events (TEAEs) including infusion site, hypersensitivity reactions and hypoglycemic events, and safety.
The number of patients reporting at least one ISO was small: 6/25 patients on SAR-Lis reported 14 ISOs and 4/27 on Ly-Lis reported nine ISOs. The estimated difference in ISO risk for SAR-Lis versus Ly-Lis was 7.9% (95% CI, -1.90 to 17.73). Mean interval between infusion set changes for any reason was similar with SAR-Lis (3.09 days) and Ly-Lis (2.95 days). The event rate (events/patient-month) of any hypoglycemia was similar with SAR-Lis (7.15) and Ly-Lis (7.98), as was the percentage of patients who experienced any TEAE (12.0% and 14.8%).
Both SAR-Lis and Ly-Lis were well tolerated by patients using insulin pumps. The results do not suggest a clinically significant difference in the risk of ISO between SAR-Lis and Ly-Lis when used in CSII.
SAR342434（U100；SAR-赖脯胰岛素）是赖脯胰岛素（U100；礼来-赖脯胰岛素）的生物类似药/后续产品。在一项高胰岛素正常血糖钳夹研究中已证明两种产品之间具有相似的药代动力学/药效学。本研究评估了通过持续皮下胰岛素输注（CSII；胰岛素泵）给药时SAR-赖脯胰岛素和礼来-赖脯胰岛素的安全性。
这是一项针对27例1型糖尿病患者的随机、开放标签、2×4周、双臂交叉研究（NCT02603510）。主要结局是输注装置堵塞（ISO）的发生率，定义为通过胰岛素泵推注胰岛素在60分钟内未能将高血糖（血浆葡萄糖≥300mg/dl）纠正50mg/dl。次要结局包括输注装置更换间隔、治疗中出现的不良事件（TEAE），包括输注部位、过敏反应和低血糖事件，以及安全性。
报告至少一次ISO的患者数量较少：使用SAR-赖脯胰岛素的25例患者中有6例报告了14次ISO，使用礼来-赖脯胰岛素的27例患者中有4例报告了9次ISO。SAR-赖脯胰岛素与礼来-赖脯胰岛素相比，ISO风险的估计差异为7.9%（95%CI，-1.90至17.73）。因任何原因进行输注装置更换的平均间隔在SAR-赖脯胰岛素（3.09天）和礼来-赖脯胰岛素（2.95天）之间相似。任何低血糖的事件发生率（事件/患者-月）在SAR-赖脯胰岛素（7.15）和礼来-赖脯胰岛素（7.98）之间相似，经历任何TEAE的患者百分比（12.0%和14.8%）也相似。
使用胰岛素泵的患者对SAR-赖脯胰岛素和礼来-赖脯胰岛素的耐受性均良好。结果表明，在CSII中使用时，SAR-赖脯胰岛素和礼来-赖脯胰岛素之间的ISO风险在临床上无显著差异。
