基于FAERS真实世界数据的替尔泊肽相关酮症酸中毒风险与特征分析及病例回顾

Analysis of the risk and characteristics of tirzepatide-associated ketoacidosis based on FAERS database and real-world cases

摘要

目的: 基于真实世界数据,探讨替尔泊肽所致酮症酸中毒的临床特征与危险因素,为临床安全用药提供参考。方法: 系统检索建库至2025年8月31日的中英文文献数据库,收集替尔泊肽相关酮症酸中毒个案报告;并提取美国FDA不良事件报告系统(FDA Adverse Event Reporting System,FAERS)2004年1月—2025年6月期间的相关数据。采用报告比值比法(reporting odds ratio,ROR)进行信号检测,并对人口学特征、用药信息、临床表现及转归进行描述性统计分析。结果: 共纳入14篇个案报道及FAERS数据库中的229例报告。女性患者占比更高(个案报道中为78.57%,FAERS中为51.96%)。酮症酸中毒多发生于用药初期(中位时间5周),临床表现主要为恶心、呕吐、腹痛、脱水及代谢性酸中毒。信号检测显示,替尔泊肽与各类酮症酸中毒均存在显著关联,尤其是饥饿性酮症酸中毒(ROR=107.36,95%CI: 71.75~160.63)和正常血糖性糖尿病酮症酸中毒(ROR=3.52,95%CI: 2.51~4.93)。联合用药中钠-葡萄糖协同转运蛋白2抑制剂(sodium-glucose co-transporter 2 inhibitors,SGLT-2i)的使用频率最高(52例)。多数患者经停药及对症支持治疗后预后良好,但FAERS数据库中报告了4例死亡事件。结论: 替尔泊肽与酮症酸中毒之间存在明确关联性,尤其好发于女性、非糖尿病状态以及联用SGLT-2i的患者。建议在临床用药过程中加强监测与患者教育,早期识别高危人群并采取干预措施,以降低严重代谢不良事件的发生风险。

Abstract

Objective: To analyze the clinical features and risk factors of tirzepatide-associated ketoacidosis using real-world data, thereby providing evidence for safer clinical use. Methods: A systematic literature search was conducted in both Chinese and English databases from inception until August 31, 2025, to identify case reports on tirzepatide-induced ketoacidosis. Data were also extracted from the FDA Adverse Event Reporting System (FAERS) spanning January 2004 to June 2025. Disproportionality analysis using the reporting odds ratio (ROR) was employed for signal detection, and descriptive statistics was applied to summarize the demographic, clinical, treatment, and outcome variables. Results: Fourteen published case reports and 229 cases from the FAERS were included. A higher proportion of cases occurred in females (78.57% in case reports; 51.96% in FAERS). Ketoacidosis often developed early during treatment (median time: 5 weeks), with common clinical features including nausea, vomiting, abdominal pain, dehydration, and metabolic acidosis. Significant signals were detected linking tirzepatide to various forms of ketoacidosis, particularly starvation ketoacidosis (ROR=107.36, 95%CI: 71.75~160.63) and euglycemic diabetic ketoacidosis (ROR=3.52, 95%CI: 2.51~4.93). Concomitant use of sodium-glucose co-transporter 2 inhibitors (SGLT-2i) was most frequently reported (52 cases). Most patients recovered after drug discontinuation and supportive care, although four fatal cases were documented in FAERS. Conclusion: Tirzepatide is associated with a significant risk of ketoacidosis, particularly in female patients, non-diabetic state, and those using SGLT-2i concurrently. Enhanced vigilance, patient education, and early intervention are recommended to mitigate the risk of serious metabolic adverse events.

关键词

替尔泊肽 / 酮症酸中毒 / 药物不良反应 / FAERS数据库

Key words

tirzepatide / ketoacidosis / adverse drug reaction / FAERS database

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