胰高血糖素样肽-1受体激动剂在家族性部分脂肪营养不良患者非对照环境中的安全性和有效性：来自国家参考网络的真实生活经验。
Safety and effectiveness in an uncontrolled setting of glucagon-like-peptide-1 receptor agonists in patients with familial partial lipodystrophy: Real-life experience from a national reference network.
作者信息
Lamothe Sophie, Belalem Ines, Vantyghem Marie-Christine, Nobecourt Estelle, Mosbah Héléna, Béliard Sophie, Delemer Brigitte, Dupuis Hippolyte, Vandenbroere Paul, Scheyer Nicolas, Amouyal Chloé, Hadjadj Samy, Janmaat Sonja, Vigouroux Corinne, Vatier Camille
机构信息
Endocrinology Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Saint-Antoine University Hospital, National Reference Centre for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France.
Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, University of Lille, INSERM U1190, European Genomic Institute for Diabetes, Lille, France.
出版信息
Diabetes Obes Metab. 2025 Apr;27(4):1815-1825. doi: 10.1111/dom.16175. Epub 2025 Jan 20.
AIM
To describe the effects of Glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with familial partial lipodystrophy (FPLD) assessed in a real-life setting in a national reference network.
PATIENTS AND METHODS
We retrospectively collected clinical and metabolic parameters in patients with FPLD in the French lipodystrophy reference network, who initiated GLP-1RA. Data were recorded before, at one-year (12 ± 6 months) and at the latest follow-up on GLP-1RA therapy (≥18 months).
RESULTS
Seventy-six patients (89.4% of women), diagnosed with LMNA-related FPLD2 (n = 57), PPARG-related FPLD3 (n = 4), PLIN1-related FPLD4 (n = 5) or FPLD1 (n = 10) initiated GLP-1RA therapy between 2008 and 2024. Patients were aged a median (IQR) 48 years (34.5-57), body mass index (BMI) was 26.0 kg/m (23.9-29.5), HbA1c 8.3% (7.5-9.3), triglycerides 2.31 mmol/L (1.62-3.88). GLP-1RA were used in addition to previously used antidiabetics, 50% of patients being insulin-treated. After one year with GLP-1RA therapy, BMI, HbA1c and triglycerides significantly decreased to 25.6 kg/m (22.7-29.1), 7.3% (6.6-8.3) and 1.97 mmol/L (1.5-3.2) respectively (p < 0.001, p < 0.001 and p < 0.01, respectively), without significant changes in other antidiabetic and lipid-lowering drugs. Gamma-glutamyl-transferase and alanine-aminotransferase levels also significantly decreased. Effects on HbA1c, BMI and triglycerides persisted in the long term. One case of acute pancreatitis occurred during follow-up, associated with severe hypertriglyceridemia in a non-observant patient. Gastrointestinal symptoms affected 34% of patients, leading to GLP-1RA withdrawal in six patients.
CONCLUSION
GLP-1RA significantly improved BMI, HbA1c and triglycerides in a large majority of patients with FPLD. Larger and prospective controlled studies are warranted for identification of predictive factors and safety.
目的
描述胰高血糖素样肽-1受体激动剂（GLP-1RA）在国家参考网络的实际临床环境中评估的家族性部分脂肪营养不良（FPLD）患者中的疗效。
患者和方法
我们回顾性收集了法国脂肪营养不良参考网络中开始使用GLP-1RA的FPLD患者的临床和代谢参数。在开始GLP-1RA治疗前、治疗一年（12±6个月）以及最新随访（≥18个月）时记录数据。
结果
76例患者（89.4%为女性）被诊断为与LMNA相关的FPLD2（n = 57）、与PPARG相关的FPLD3（n = 4）、与PLIN1相关的FPLD4（n = 5）或FPLD1（n = 10），于2008年至2024年间开始GLP-1RA治疗。患者年龄中位数（IQR）为48岁（34.5 - 57岁），体重指数（BMI）为26.0kg/m²（23.9 - 29.5），糖化血红蛋白（HbA1c）为8.3%（7.5 - 9.3），甘油三酯为2.31mmol/L（1.62 - 3.88）。GLP-1RA是在先前使用的抗糖尿病药物基础上加用的，50%的患者接受胰岛素治疗。GLP-1RA治疗一年后，BMI、HbA1c和甘油三酯分别显著降至25.6kg/m²（22.7 - 29.1）、7.3%（6.6 - 8.3）和1.97mmol/L（1.5 - 3.2）（p均<0.001），其他抗糖尿病和降脂药物无显著变化。γ-谷氨酰转移酶和丙氨酸氨基转移酶水平也显著降低。对HbA1c、BMI和甘油三酯的影响长期持续。随访期间发生1例急性胰腺炎，与1例未严格遵医嘱的患者严重高甘油三酯血症有关。34%的患者出现胃肠道症状，6例患者因此停用GLP-1RA。
结论
GLP-1RA在大多数FPLD患者中显著改善了BMI、HbA1c和甘油三酯水平。需要开展更大规模的前瞻性对照研究以确定预测因素和安全性。
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