Division of Pharmacovigilance, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Division of Pharmacovigilance, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Endocr Pract. 2024 Jul;30(7):603-609. doi: 10.1016/j.eprac.2024.04.012. Epub 2024 Apr 29.
To describe reported cases of prolonged or relapsed ketoacidosis (KA) in adults with type 2 diabetes receiving treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors.
We performed a search of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and medical literature, to identify our case series and to characterize cases of prolonged KA, relapsed KA, or persistent ketonemia, persistent ketonuria and/or persistent glucosuria in adults receiving SGLT2 inhibitors.
The FDA identified 29 unique cases of prolonged or relapsed KA, as well as related terms persistent ketonemia, persistent ketonuria, and persistent glucosuria, in patients receiving SGLT2 inhibitors through July 26, 2022. The patients ranged in age from 26 to 85 years. Treatment duration of KA ranged from 3 to 20 days. There were 7 cases of relapsed KA when insulin was reduced or transitioned to subcutaneous route. Arterial pH value was 7.0 or below in 4 patients, and the median pH was 7.1. Associated factors for prolonged or relapsed KA included surgery, decreased caloric intake, and ketogenic/carbohydrate restricted diet. A total of 62% of the patients were taking 3 or more glycemic control medications including the SGLT2 inhibitor. All patients with sufficient follow-up information recovered.
Although KA is a well-known risk associated with SGLT2 inhibitors, this case series demonstrated the potential for prolonged or recurrent KA events with serious outcomes. These cases informed updates to FDA's prescribing information to inform prescribers of this risk.
描述接受钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂治疗的 2 型糖尿病成人患者出现延长或复发酮症酸中毒（KA）的报告病例。
我们对美国食品和药物管理局（FDA）不良事件报告系统和医学文献进行了检索，以确定我们的病例系列，并对接受 SGLT2 抑制剂治疗的成人患者中出现的延长性 KA、复发性 KA 或持续性酮血症、持续性酮尿症和/或持续性糖尿进行特征描述。
截至 2022 年 7 月 26 日，FDA 通过在 FDA 不良事件报告系统中识别出 29 例接受 SGLT2 抑制剂治疗的患者出现了独特的延长或复发性 KA 以及相关术语持续性酮血症、持续性酮尿症和持续性糖尿。患者年龄在 26 至 85 岁之间。KA 的治疗持续时间从 3 天到 20 天不等。有 7 例 KA 复发是在减少胰岛素用量或转为皮下途径时发生的。4 名患者的动脉 pH 值为 7.0 或以下，中位数 pH 值为 7.1。延长或复发性 KA 的相关因素包括手术、热量摄入减少和生酮/低碳水化合物饮食。总共 62%的患者正在服用 3 种或更多种血糖控制药物，包括 SGLT2 抑制剂。所有有足够随访信息的患者均康复。
尽管 KA 是与 SGLT2 抑制剂相关的已知风险，但本病例系列表明存在与严重结局相关的延长或复发性 KA 事件的潜在风险。这些病例为 FDA 的用药信息更新提供了信息，以告知临床医生这一风险。
