Chen Jieling, Borra Sujana, Huang Ahong, Fan Ludi, Pollom Roy Daniel, Hood Robert C
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
STATinMED Research, Plano, TX, USA.
Diabetes Ther. 2022 Mar;13(3):465-479. doi: 10.1007/s13300-022-01209-z. Epub 2022 Feb 21.
Humulin R U-500 (U-500R) utilization has increased in the past few years, raising concerns as U-500R is indicated only for patients requiring > 200 units of insulin. Thus, evidence of dispensed total daily dose (dTDD) > 200 units of prior U-100 insulin based on pharmacy claims is increasingly used as a criterion to determine appropriate switching to U-500R by payers. The study compared the treatment patterns and outcomes before and after U-500R initiation among patients who were identified with ≤ 200 units/day U-100 insulin fill in order to understand the appropriateness of switching.
Patients with type 2 diabetes who initiated U-500R (index date = first fill) with ≤ 200 units/day pre-index dTDD and > 200 units/day post-index dTDD were identified in a Veterans Health Administration dataset between 1 January 2014 and 30 June 2017. Descriptive analysis was conducted on treatment patterns (dTDD, insulin dosage [units/kg], adherence, number of prescription fills) and clinical outcomes (HbA1c, symptomatic hypoglycemic events). Associations between U-500R exposure and outcomes were evaluated using mixed-effects models. Subgroups of U-500R syringe and KwikPen users were analyzed separately.
Among 1191 U-500R initiators identified in the study the mean dTDD increased from the pre- to post-index periods (147.2 vs 346.3; p < 0.0001). The mean HbA1c decreased from pre- to post-initiation (9.6% vs 8.6%; p < 0.0001), and symptomatic hypoglycemia events per patient per year increased (2.0 vs 3.3, p < 0.0001). Mixed-effects models confirmed the significance of the changes (p < 0.0001). Device subgroups followed similar trends.
U-500R initiation was associated with large dTDD increases, improved glycemic control, and modest increases in hypoglycemia events, suggesting U-500R initiation may have corrected previous treatment compliance issues. Imposing dTDDs > 200 units before switching to U-500R criterion could hurt the opportunities for patients who need a simplified regimen for better outcomes.
在过去几年中，优泌林R U-500（U-500R）的使用有所增加，这引发了人们的担忧，因为U-500R仅适用于需要超过200单位胰岛素的患者。因此，基于药房报销记录的既往U-100胰岛素每日总剂量（dTDD）超过200单位的证据越来越多地被支付方用作确定是否适合改用U-500R的标准。本研究比较了起始使用U-500R之前和之后，每日U-100胰岛素填充量≤200单位的患者的治疗模式和结局，以了解改用U-500R的合理性。
在退伍军人健康管理局的数据集中，识别出2014年1月1日至2017年6月30日期间起始使用U-500R（索引日期=首次填充），索引日期前dTDD≤200单位/天且索引日期后dTDD>200单位/天的2型糖尿病患者。对治疗模式（dTDD、胰岛素剂量[单位/千克]、依从性、处方填充次数）和临床结局（糖化血红蛋白、有症状低血糖事件）进行描述性分析。使用混合效应模型评估U-500R暴露与结局之间的关联。分别分析使用U-500R注射器和笔芯的亚组。
在本研究中识别出的1191名起始使用U-500R的患者中，平均dTDD从索引日期前到索引日期后有所增加（147.2对346.3；p<0.0001）。平均糖化血红蛋白从起始前到起始后有所下降（9.6%对8.6%；p<0.0001），且每位患者每年的有症状低血糖事件有所增加（2.0对3.3，p<0.0001）。混合效应模型证实了这些变化具有统计学意义（p<0.0001）。不同器械亚组呈现相似趋势。
起始使用U-500R与dTDD大幅增加、血糖控制改善以及低血糖事件适度增加相关，这表明起始使用U-500R可能纠正了先前的治疗依从性问题。在改用U-500R标准之前设定dTDD>200单位可能会损害那些需要简化治疗方案以获得更好结局的患者的机会。
