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成功治疗纳武利尤单抗和伊匹单抗引发的 1 型糖尿病:病例报告和系统评价。

Successful treatment of nivolumab and ipilimumab triggered type 1 diabetes by using sodium-glucose transporter 2 inhibitor: a case report and systematic review.

机构信息

Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University School of Medicine, Fukushima, Japan.

Department of Diabetes, Endocrinology and Metabolism, Tsukuba Medical Center, Ibaraki, Japan.

出版信息

Front Public Health. 2023 Dec 1;11:1264056. doi: 10.3389/fpubh.2023.1264056. eCollection 2023.

Abstract

OBJECTIVE

Checkpoint inhibitors (CPIs) can trigger complications related to the autoimmune process such as CPI-triggered diabetes mellitus. The typical treatment for CPI-triggered diabetes is insulin, but a detailed therapeutic method has not yet been established. To prevent severe symptoms and mortality of diabetic ketoacidosis in advanced-stage cancer patients, the establishment of effective treatment of CPI-triggered diabetes, other than insulin therapy, is required.

METHODS

We present a case of a 76-year-old man with CPI-triggered diabetes who was treated with nivolumab and ipilimumab for lung cancer. We also conducted a systematic review of 48 case reports of type 1 diabetes associated with nivolumab and ipilimumab therapy before June 2023.

RESULTS

The patient's hyperglycemia was not sufficiently controlled by insulin therapy, and after the remission of ketoacidosis, the addition of a sodium-glucose transporter (SGLT) 2 inhibitor, dapagliflozin, improved glycemic control. Most of the reported nivolumab/ipilimumab-induced type 1 diabetes was treatable with insulin, but very few cases required additional oral anti-diabetic agents to obtain good glucose control.

CONCLUSION

Although SGLT2 inhibitors have been reported to have adverse effects on ketoacidosis, recent studies indicate that the occurrence of ketoacidosis is relatively rare. Considering the pathological mechanism of CPI-triggered diabetes, SGLT2 inhibitors could be an effective choice if they are administered while carefully monitoring the patient's ketoacidosis.

摘要

目的

检查点抑制剂(CPIs)可引发与自身免疫过程相关的并发症,如 CPI 引发的糖尿病。CPI 引发的糖尿病的典型治疗方法是胰岛素,但尚未建立详细的治疗方法。为了预防晚期癌症患者糖尿病酮症酸中毒的严重症状和死亡率,需要建立除胰岛素治疗以外的 CPI 引发的糖尿病的有效治疗方法。

方法

我们报告了一例 76 岁男性患者,他因肺癌接受了纳武利尤单抗和伊匹单抗治疗。我们还对截至 2023 年 6 月之前与纳武利尤单抗和伊匹单抗治疗相关的 48 例 1 型糖尿病病例报告进行了系统回顾。

结果

患者的高血糖不能通过胰岛素治疗充分控制,在酮症酸中毒缓解后,加用钠-葡萄糖共转运蛋白(SGLT)2 抑制剂达格列净,改善了血糖控制。大多数报告的纳武利尤单抗/伊匹单抗诱导的 1 型糖尿病可通过胰岛素治疗,但很少有病例需要额外的口服降糖药来获得良好的血糖控制。

结论

尽管 SGLT2 抑制剂已被报道可引起酮症酸中毒的不良反应,但最近的研究表明,酮症酸中毒的发生相对较少。考虑到 CPI 引发的糖尿病的病理机制,如果在仔细监测患者的酮症酸中毒的情况下使用,SGLT2 抑制剂可能是一种有效的选择。

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