Drug-Associated Ketoacidosis: A Comprehensive Disproportionality Analysis Based on the FAERS Database

Area of Science:

• Pharmacovigilance
• Drug Safety
• Adverse Event Analysis

Background:

• Ketoacidosis is a serious adverse event requiring vigilant clinical observation.
• Identifying drugs associated with ketoacidosis is crucial for patient safety.

Purpose of the Study:

• To identify drugs most strongly associated with drug-induced ketoacidosis using disproportionality analysis.
• To provide a reference for enhancing clinical medication safety and monitoring.

Main Methods:

• Utilized the FDA's FAERS database (Q1 2004 - Q2 2025) for adverse event reports.
• Employed disproportionality analyses (ROR, PRR, IC) and Time-to-Onset (TTO) analysis.
• Standardized drug names using DrugBank and MedDRA for outcome indicators.

Main Results:

• Analyzed over 22 million adverse event reports, with 6,977 related to ketoacidosis.
• Top drugs by report count: metformin, quetiapine, empagliflozin, canagliflozin, dapagliflozin.
• Significant association found with SGLT2 inhibitors (e.g., dapagliflozin) and psychotropic drugs (e.g., quetiapine).
• 72% of top ROR drugs lacked ketoacidosis warnings in package inserts.
• TTO analysis revealed varying onset patterns for different drug classes.

Conclusions:

• Sodium-glucose cotransporter 2 (SGLT2) inhibitors and psychotropic drugs are primary risks for ketoacidosis.
• Undocumented ketoacidosis risks in package inserts necessitate increased clinical attention.
• Study findings support improved medication monitoring and potential updates to drug labeling.