Gadelha Mônica R, Gu Feng, Bronstein Marcello D, Brue Thierry C, Fleseriu Maria, Shimon Ilan, van der Lely Aart J, Ravichandran Shoba, Kandra Albert, Pedroncelli Alberto M, Colao Annamaria A L
Endocrine Unit, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, China.
Endocr Connect. 2020 Dec;9(12):1178-1190. doi: 10.1530/EC-20-0361.
Pasireotide, a multireceptor-targeted somatostatin analog with highest affinity for somatostatin receptor subtype (SST) 5, has demonstrated superior efficacy over the SST2-preferential somatostatin analogs octreotide and lanreotide. The safety profile is similar to those of octreotide and lanreotide, except for a higher frequency and degree of hyperglycemia. This analysis investigated baseline characteristics and occurrence and management of hyperglycemia during pasireotide treatment in patients with acromegaly treated in two prospective clinical studies, SOM230C2305 (C2305) and SOM230C2402 (C2402; PAOLA). One hundred and seventy-eight patients naïve to medical therapy at baseline (C2305) and 125 uncontrolled on first-generation somatostatin analogs at baseline (C2402) received long-acting pasireotide in these studies. Of patients treated with pasireotide in studies C2305 and C2402, respectively, 75.3 (134/178) and 65.6% (82/125) developed hyperglycemia or experienced worsening of existing hyperglycemia. Occurrence of hyperglycemia during pasireotide treatment was less frequent in patients with lower age (<40 years, C2402; <30 years, C2305), normal glucose tolerance, and no history of hypertension or dyslipidemia at baseline. Thirteen (4%) patients discontinued pasireotide because of hyperglycemia-related adverse events. Metformin alone or in combination with other oral antidiabetic medications controlled elevations in glucose levels in most pasireotide-treated patients; 78% of C2305 patients and 73 (pasireotide 40 mg) and 60% (pasireotide 60 mg) of C2402 patients achieved the ADA/EASD goal of HbA1c <7% (<53 mmol/mol) at the end of the core phase. Not all patients develop hyperglycemia, and it is reversible upon pasireotide withdrawal. Close monitoring, patient education and prompt action remain key elements in addressing hyperglycemia during pasireotide treatment.
帕西瑞肽是一种多受体靶向生长抑素类似物，对生长抑素受体亚型（SST）5具有最高亲和力，已证明其疗效优于优先靶向SST2的生长抑素类似物奥曲肽和兰瑞肽。其安全性与奥曲肽和兰瑞肽相似，只是高血糖的发生频率和程度更高。该分析在两项前瞻性临床研究SOM230C2305（C2305）和SOM230C2402（C2402；PAOLA）中，调查了肢端肥大症患者接受帕西瑞肽治疗期间的基线特征、高血糖的发生情况及处理方法。在这些研究中，178例基线时未接受过药物治疗的患者（C2305）和125例基线时第一代生长抑素类似物治疗未达标的患者（C2402）接受了长效帕西瑞肽治疗。在C2305和C2402研究中接受帕西瑞肽治疗的患者中，分别有75.3%（134/178）和65.6%（82/125）出现高血糖或原有高血糖病情加重。帕西瑞肽治疗期间，年龄较小（C2402中<40岁；C2305中<30岁）、葡萄糖耐量正常且基线无高血压或血脂异常病史的患者高血糖发生率较低。13例（4%）患者因高血糖相关不良事件停用帕西瑞肽。在大多数接受帕西瑞肽治疗的患者中，单独使用二甲双胍或与其他口服抗糖尿病药物联合使用可控制血糖水平升高；在核心阶段结束时，C2305研究中78%的患者以及C2402研究中73%（帕西瑞肽40mg组）和60%（帕西瑞肽60mg组）的患者达到了ADA/EASD设定的糖化血红蛋白<7%（<53mmol/mol）的目标。并非所有患者都会发生高血糖，且停用帕西瑞肽后高血糖是可逆的。密切监测、患者教育以及及时采取措施仍然是处理帕西瑞肽治疗期间高血糖问题的关键要素。
