Miyoshi Hideaki, Matsuhisa Munehide, Yabe Daisuke, Takahashi Yoko, Morimoto Yukiko, Terauchi Yasuo
Department of Immunology and Metabolism, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
Diabetes Ther. 2023 Apr;14(4):671-689. doi: 10.1007/s13300-023-01373-w. Epub 2023 Feb 21.
iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide 1 receptor agonist (GLP-1 RA) lixisenatide, is one option for treatment intensification in individuals with type 2 diabetes (T2D) who are unable to achieve targeted glycaemic control with their current glucose-lowering agent. Real-world data on the impact of prior treatment on the effectiveness and safety of iGlarLixi may be useful to guide individualised treatment decisions.
This analysis of the 6-month, retrospective, observational SPARTA Japan study compared glycated haemoglobin (HbA1c), body weight and safety for pre-specified subgroups defined by prior treatment: post oral antidiabetic agent (OAD), GLP-1 RA, basal insulin (BI) + OADs (BOT), GLP-1 RA + BI or multiple daily injections (MDI). The post BOT and MDI subgroups were further divided on the basis of prior dipeptidyl peptidase 4 inhibitor (DPP-4i) use, and the post MDI group was divided on the basis of whether participants continued bolus insulin.
Of the 432 participants in the full analysis set (FAS), 337 were included in this subgroup analysis. Across subgroups, mean baseline HbA1c ranged from 8.49% to 9.18%. iGlarLixi significantly (p < 0.05) reduced mean HbA1c from baseline in all but the post GLP-1 RA + BI group. At 6 months, these significant reductions ranged from 0.47% to 1.27%. Prior DPP-4i exposure had no impact on the HbA1c-lowering effect of iGlarLixi. Mean body weight decreased significantly in the FAS (0.5 kg) and the post BOT (1.2 kg) and MDI (1.5 and 1.9 kg) subgroups but increased in the post GLP-1 RA subgroup (1.3 kg). iGlarLixi treatment was generally well tolerated, with very few participants discontinuing because of hypoglycaemia or gastrointestinal events.
In participants with suboptimal glycaemic control on various regimens, 6 months of iGlarLixi treatment improved HbA1c in all but one prior treatment subgroup (GLP-1 RA + BI), and was generally well tolerated.
UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.
iGlarLixi是一种固定比例组合药物，由100 U/mL的甘精胰岛素和胰高血糖素样肽-1受体激动剂（GLP-1 RA）利司那肽组成，是2型糖尿病（T2D）患者强化治疗的一种选择，这些患者使用当前降糖药物无法实现目标血糖控制。关于既往治疗对iGlarLixi有效性和安全性影响的真实世界数据可能有助于指导个体化治疗决策。
这项对为期6个月的回顾性观察性SPARTA日本研究的分析，比较了根据既往治疗定义的预先指定亚组的糖化血红蛋白（HbA1c）、体重和安全性：口服抗糖尿病药物（OAD）治疗后、GLP-1 RA治疗后、基础胰岛素（BI）+OADs（BOT）治疗后、GLP-1 RA+BI或多次皮下注射（MDI）治疗后。BOT治疗后和MDI治疗后的亚组根据既往二肽基肽酶4抑制剂（DPP-4i）的使用情况进一步划分，MDI治疗后的组根据参与者是否继续使用餐时胰岛素进行划分。
在全分析集（FAS）的432名参与者中，337名被纳入该亚组分析。在各个亚组中，平均基线HbA1c范围为8.49%至9.18%。除GLP-1 RA+BI治疗后组外，iGlarLixi在所有亚组中均显著（p<0.05）降低了HbA1c均值。在6个月时，这些显著降低的幅度为0.47%至1.27%。既往DPP-4i暴露对iGlarLixi降低HbA1c的效果没有影响。FAS组（0.5 kg）、BOT治疗后组（1.2 kg）和MDI治疗后组（1.5 kg和1.9 kg）的平均体重显著下降，但GLP-1 RA治疗后组的平均体重增加（1.3 kg）。iGlarLixi治疗总体耐受性良好，因低血糖或胃肠道事件停药的参与者很少。
在各种治疗方案下血糖控制不佳的参与者中，6个月的iGlarLixi治疗改善了除一个既往治疗亚组（GLP-1 RA+BI）外所有亚组的HbA1c，且总体耐受性良好。
UMIN-CTR试验注册中心，UMIN000044126；2021年5月10日注册。
