National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Internal Medicine, University of Michigan Medical School and Health Systems, Ann Arbor, MI, USA.
Endocrine. 2018 Jun;60(3):479-489. doi: 10.1007/s12020-018-1589-1. Epub 2018 Apr 12.
The purpose of this study is to summarize the effectiveness and safety of metreleptin in patients with congenital or acquired generalized lipodystrophy.
Patients (n = 66) aged ≥6 months had lipodystrophy, low circulating leptin, and ≥1 metabolic abnormality (diabetes mellitus, insulin resistance, or hypertriglyceridemia). Metreleptin dose (once or twice daily) was titrated to a mean dose of 0.10 mg/kg/day with a maximum of 0.24 mg/kg/day. Means and changes from baseline to month 12 were assessed for glycated hemoglobin (HbA1c), fasting triglycerides (TGs), and fasting plasma glucose (FPG). Additional assessments included the proportions of patients achieving target decreases in HbA1c or fasting TGs at months 4, 12, and 36, medication changes, and estimates of liver size. Treatment-emergent adverse events (TEAEs) were recorded.
Significant mean reductions from baseline were seen at month 12 for HbA1c (-2.2%, n = 59) and FPG (-3.0 mmol/L, n = 59) and mean percent change in fasting TGs (-32.1%, n = 57) (all p ≤ 0.001). Reductions from baseline over time in these parameters were also significant at month 36 (all p < 0.001, n = 14). At month 4, 34.8% of patients had a ≥1% reduction in HbA1c and 62.5% had a ≥30% reduction in fasting TGs; at month 12, 80% of patients had a ≥1% decrease in HbA1c or ≥30% decrease in TGs, and 66% had a decrease of ≥2% in HbA1c or ≥40% decrease in TGs. Of those on medications, 41%, 22%, and 24% discontinued insulin, oral antidiabetic medications, or lipid-lowering medications, respectively. Mean decrease in liver volume at month 12 was 33.8% (p < 0.001, n = 12). Most TEAEs were of mild/moderate severity.
In patients with generalized lipodystrophy, long-term treatment with metreleptin was well tolerated and resulted in sustained improvements in hypertriglyceridemia, glycemic control, and liver volume.
本研究旨在总结 metreleptin 在先天性或获得性全身性脂肪营养不良患者中的疗效和安全性。
年龄≥6 个月的患者存在脂肪营养不良、循环瘦素水平低和≥1 种代谢异常（糖尿病、胰岛素抵抗或高甘油三酯血症）。Metreleptin 剂量（每日一次或两次）滴定至平均 0.10mg/kg/天，最大剂量为 0.24mg/kg/天。评估糖化血红蛋白（HbA1c）、空腹甘油三酯（TGs）和空腹血糖（FPG）自基线至 12 个月的平均值和变化。其他评估包括达到 HbA1c 或空腹 TGs 目标降低的患者比例（4、12 和 36 个月）、药物变化和肝大小估计。记录治疗出现的不良事件（TEAEs）。
在 12 个月时，HbA1c（-2.2%，n=59）和 FPG（-3.0mmol/L，n=59）显著低于基线，空腹 TGs 平均百分比变化（-32.1%，n=57）（均 p≤0.001）。在 36 个月时，这些参数的时间变化也具有显著意义（均 p<0.001，n=14）。在 4 个月时，34.8%的患者 HbA1c 降低≥1%，62.5%的患者空腹 TGs 降低≥30%；在 12 个月时，80%的患者 HbA1c 降低≥1%或 TGs 降低≥30%，66%的患者 HbA1c 降低≥2%或 TGs 降低≥40%。在使用药物的患者中，分别有 41%、22%和 24%的患者停用胰岛素、口服降糖药或降脂药。12 个月时肝脏体积的平均减少量为 33.8%（p<0.001，n=12）。大多数 TEAEs 为轻度/中度严重程度。
在全身性脂肪营养不良患者中，长期使用 metreleptin 治疗耐受良好，可持续改善高甘油三酯血症、血糖控制和肝脏体积。
