Department of Internal Medicine, Endocrinology and Diabetes, Mazovian Bródno Hospital, Medical University of Warsaw, Warsaw, Poland.
Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland.
Front Endocrinol (Lausanne). 2021 Mar 10;12:633944. doi: 10.3389/fendo.2021.633944. eCollection 2021.
The aim of the study was to evaluate glucose metabolism, as measured by glycated hemoglobin (HbA1c) levels and the need for antidiabetic medical treatment, in patients with acromegaly resistant to first-generation somatostatin receptors ligands (SRLs) treated with pasireotide long-acting release (LAR) in real-world clinical practice. Biochemical control of acromegaly, as measured by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, was also assessed.
Two-center retrospective cohort of consecutive patients with acromegaly treated with first-generation SRLs at maximum doses, who had not achieved biochemical disease control. After SRLs were discontinued, patients were given pasireotide LAR 40 mg i.m. every 28 days. The dose was increased to 60 mg i.m. in patients for whom adequate control was not achieved after 3 months. Patients were given dietary and lifestyle advice, and antihyperglycemic treatment was modified as needed.
Biochemical disease control parameters (GH and IGF-1 concentration), as well as HbA1c level at baseline and after 6 months.
In total, 39 patients with acromegaly were enrolled. GH concentration decreased (Δ =-1.56 µg/L, range -21.38-3.62, p <0.001) during 6 months of pasireotide LAR treatment. A worsening of metabolic status was observed, with an increase of median HbA1c (Δ =0.40%, range -0.20%-2.30%, p <0.001), and antihyperglycemic treatment intensification in 23 (59.0%) patients. The median decline in IGF-1 concentration was: -283.0 µg/L, range -682.7-171.6, p <0.001. IGF-1 reached the age- and gender-specific upper level of normal in 23 (59%) patients.
Pasireotide LAR is an effective therapeutic option in patients with acromegaly refractory to first-generation SRLs. However, this therapy may result in pasireotide LAR-associated hyperglycemia, which requires early and aggressive antidiabetic medical therapy to prevent glucose homeostasis alterations.
本研究旨在评估在第一代生长抑素受体配体（SRLs）治疗抵抗的肢端肥大症患者中，使用帕瑞肽长效释放剂（LAR）治疗后，糖化血红蛋白（HbA1c）水平和抗糖尿病药物治疗需求所反映的葡萄糖代谢变化。同时也评估了肢端肥大症的生化控制情况，通过生长激素（GH）和胰岛素样生长因子 1（IGF-1）水平来衡量。
对在最大剂量下接受第一代 SRLs 治疗但未达到生化疾病控制的连续肢端肥大症患者进行了一项两中心回顾性队列研究。停用 SRLs 后，患者每 28 天接受一次 40 mg 肌肉注射帕瑞肽 LAR。如果 3 个月后仍未达到充分控制，则将剂量增加至 60 mg 肌肉注射。患者还接受了饮食和生活方式建议，并且根据需要调整了抗高血糖治疗。
生化疾病控制参数（GH 和 IGF-1 浓度）以及基线和 6 个月时的 HbA1c 水平。
共纳入 39 例肢端肥大症患者。帕瑞肽 LAR 治疗 6 个月时，GH 浓度降低（Δ=-1.56 µg/L，范围-21.38-3.62，p<0.001）。代谢状态恶化，中位 HbA1c 升高（Δ=0.40%，范围 0.20%-2.30%，p<0.001），23 例（59.0%）患者需要加强抗高血糖治疗。IGF-1 浓度的中位下降值为：-283.0 µg/L，范围-682.7-171.6，p<0.001。23 例（59%）患者的 IGF-1 达到了年龄和性别特异性的正常上限。
帕瑞肽 LAR 是第一代 SRLs 治疗抵抗的肢端肥大症患者的有效治疗选择。然而，这种治疗方法可能导致与帕瑞肽 LAR 相关的高血糖，需要早期和积极的抗糖尿病药物治疗，以防止葡萄糖稳态改变。
