Carlsson Petri Kristin Cecilie, Ingwersen Steen Hvass, Flint Anne, Zacho Jeppe, Overgaard Rune Viig
Novo Nordisk A/S, Vandtårnsvej 108, 2860, Søborg, Denmark.
Diabetes Ther. 2018 Aug;9(4):1533-1547. doi: 10.1007/s13300-018-0458-5. Epub 2018 Jun 15.
Semaglutide, a new treatment option approved for the treatment of patients with type 2 diabetes mellitus, is a glucagon-like peptide-1 receptor agonist to be injected subcutaneously once weekly. This analysis used a population pharmacokinetic model of semaglutide to identify clinically relevant covariates for exposure.
A total of 1612 patients with up to seven pharmacokinetic observations each were included in the analysis. All subjects had type 2 diabetes mellitus and were enrolled in one of five trials in the phase III development program for subcutaneous semaglutide once weekly (the SUSTAIN program). The treatment duration of the trials varied from 30 to 104 weeks.
No clinically relevant effects on the exposure were seen for sex, age, race, ethnicity, renal function, or injection site used, and semaglutide exposure was stable over time. Of the covariates chosen, only body weight had a relevant effect on the exposure of semaglutide. Few subjects developed semaglutide antibodies, and the antibodies had no effect on exposure. Dose proportionality was shown for the 0.5 mg and 1.0 mg maintenance doses of semaglutide.
The population pharmacokinetic study showed that semaglutide exposure is not affected by covariates other than body weight at either a maintenance dose of 0.5 or 1.0 mg semaglutide. Therefore, we conclude that no semaglutide dose adjustments are needed in different populations. This finding is to be further explored in an exposure-response analysis.
The trials were registered at ClinicalTrials.gov (identifiers: NCT02054897, NCT01930188, NCT01885208, NCT01720446 and NCT02207374).
Novo Nordisk A/S, Bagsværd, Denmark.
司美格鲁肽是一种被批准用于治疗2型糖尿病患者的新治疗选择，它是一种胰高血糖素样肽-1受体激动剂，每周皮下注射一次。本分析使用司美格鲁肽的群体药代动力学模型来确定与暴露相关的临床协变量。
共有1612名患者参与分析，每名患者最多有7次药代动力学观察数据。所有受试者均患有2型糖尿病，并参加了皮下注射司美格鲁肽每周一次的III期开发项目中的五项试验之一（SUSTAIN项目）。试验的治疗持续时间从30周到104周不等。
性别、年龄、种族、民族、肾功能或注射部位对暴露均无临床相关影响，且司美格鲁肽的暴露随时间稳定。在所选择的协变量中，只有体重对司美格鲁肽的暴露有相关影响。很少有受试者产生司美格鲁肽抗体，且这些抗体对暴露没有影响。司美格鲁肽0.5毫克和1.0毫克维持剂量显示出剂量比例性。
群体药代动力学研究表明，在司美格鲁肽0.5毫克或1.0毫克维持剂量下，除体重外，其他协变量均不影响司美格鲁肽的暴露。因此，我们得出结论，不同人群无需调整司美格鲁肽剂量。这一发现有待在暴露-反应分析中进一步探索。
这些试验已在ClinicalTrials.gov注册（标识符：NCT02054897、NCT01930188、NCT01885208、NCT01720446和NCT02207374）。
丹麦 Bagsværd 的诺和诺德公司。
