Abstract

Objective

To evaluate the effects of metreleptin in distinct subgroups of patients with generalized lipodystrophy (GL) and partial lipodystrophy (PL), using multivariate linear regression modeling to account for the role of patients’ baseline usage of concomitant glucose and lipid-lowering medications and other covariates on their outcomes.

Materials and methods

A post-hoc statistical analysis of two published single-arm, interventional, phase 2 clinical trials at NIH was conducted. Concomitant medication use was assessed for the clinical trial population using prescription fill data, measured at baseline and the post-one year following metreleptin initiation. Pre-specified co-primary efficacy endpoints measured were change from baseline in HbA1c at month 12, and the percent change from baseline in fasting serum triglycerides (TG) at month 12. Descriptive and statistical analyses were conducted for the overall population, the separate populations with GL and PL, and additional PL subgroups defined by baseline metabolic markers of elevated HbA1c and elevated fasting TG.

Results

As previously reported, improvement in HbA1c and fasting TG from baseline to 12 months on metreleptin were observed in the overall population (mean change −1.57 percentage points and median change −37.9%, respectively) and subgroups. For both HbA1c and TG, baseline levels were significant predictors of changes after metreleptin. After considering baseline characteristics such as disease type, age, sex, and baseline HbA1c, baseline insulin use was not found to be a significant predictor of HbA1c improvement following metreleptin initiation. Similar results were seen for TG levels, with the use of any lipid-lowering medications at baseline not found to be a significant predictor of reductions in fasting TG levels.

Conclusions

Patients treated with metreleptin experienced statistically significant improvement in metabolic markers of glycemic and hypertriglyceridemic control—e.g. HbA1c and triglyceride levels—across various subgroups after controlling for baseline characteristics and concomitant medication usage.

中文翻译：

---

美曲普汀对有或没有基线伴随药物使用的脂肪代谢障碍患者的影响

摘要

客观的

为了评估美曲普汀对全身性脂肪代谢障碍 (GL) 和部分脂肪代谢障碍 (PL) 患者不同亚组的影响，使用多变量线性回归模型来解释患者基线使用伴随的葡萄糖和降脂药物以及其他协变量的作用关于他们的结果。

材料和方法

甲事后2出版单臂，介入，相位的统计分析在NIH 2次临床试验中进行。使用处方填充数据评估临床试验人群的伴随药物使用情况，这些数据在基线和开始使用美曲普汀后一年后测量。测量的预先指定的共同主要疗效终点是第 12 个月 HbA1c 相对于基线的变化，以及第 12 个月空腹血清甘油三酯 (TG) 相对于基线的百分比变化。 对总体人群、不同人群进行了描述性和统计分析GL 和 PL，以及由 HbA1c 升高和空腹 TG 升高的基线代谢标志物定义的其他 PL 亚组。

结果

正如之前报道的那样，在总体人群（分别为平均变化 -1.57 个百分点和中位变化 -37.9%）和亚组中观察到，从基线到服用美曲普汀 12 个月，HbA1c 和空腹 TG 的改善。对于 HbA1c 和 TG，基线水平是美曲普汀后变化的重要预测因子。在考虑疾病类型、年龄、性别和基线 HbA1c 等基线特征后，未发现基线胰岛素使用是开始使用美曲普汀后 HbA1c 改善的重要预测因素。TG 水平也出现了类似的结果，未发现基线时使用任何降脂药物是空腹 TG 水平降低的重要预测因素。

结论

在控制基线特征和伴随的药物使用后，接受美曲普汀治疗的患者在血糖和高甘油三酯控制的代谢标志物（例如 HbA1c 和甘油三酯水平）方面有统计学显着改善。