PD-1/PD-L1 inhibitor-induced metabolic and nutritional disorders: a real-world pharmacovigilance analysis using FAERS database

Background Immune checkpoint inhibitors targeting PD-1/PD-L1 have transformed oncology, yet their association with metabolic and nutritional disorders (MNDs) remains poorly characterized in real-world populations. While classic endocrine immune-related adverse events are recognized, the comprehensive spectrum, temporal dynamics, and differential risks between PD-1 and PD-L1 inhibitors require systematic elucidation to inform evidence-based monitoring strategies. Methods We conducted a retrospective pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) from Q1 2011 to Q2 2025. Reports of MNDs with eight PD-1/PD-L1 inhibitors as primary suspected drugs were identified. Disproportionality analysis employed four algorithms (ROR, PRR, BCPNN, MGPS) with concordant positivity required for signal detection. Preferred terms (PTs) were analyzed at the System Organ Class level. Time-to-onset (TTO) was characterized using Kaplan-Meier estimation and Weibull shape parameter (β) modeling to identify failure patterns. Results Among 21,712,563 total records, 5,160 MNDs reports were identified. Males (53.22%) and older adults (65–85 years, 45.19%) predominated. Disproportionality signals were detected for 29 PTs with PD-1 inhibitors versus 13 PTs with PD-L1 inhibitors. Fulminant type 1 diabetes mellitus (FT1DM) emerged as the strongest consistent signal. Nivolumab, pembrolizumab, and atezolizumab demonstrated the broadest metabolic risk spectra (24, 16, and 17 positive PTs, respectively). Weibull analysis revealed an early-failure pattern (β < 1), with 80% of events occurring within 120 days. Conclusion This study provides comprehensive real-world evidence delineating distinct metabolic toxicity profiles between PD-1 and PD-L1 inhibitors, with FT1DM as a critical early-onset complication. The concentrated risk window within initial treatment cycles supports front-loaded metabolic surveillance to enhance patient safety.