Shifa Taj, Mohammed Zuber, Muhammed Rashid, Manik Chhabra, Krishna Undela, Smita Rawal, Lorenzo Villa Zapata
Abstract Aims Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are widely used for type 2 diabetes mellitus and obesity, with once‐weekly dosing that supports adherence. However, injection‐site reactions (ISRs) and dermatologic events have been recognised, ranging from mild local events to rare systemic hypersensitivity reactions that may cause discontinuation. To evaluate dermatologic and ISR safety of GLP‐1 RAs through a meta‐analysis of randomised controlled trials (RCTs) and disproportionality analysis of data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Materials and Methods PubMed, Embase and Web of Science were searched through December 2024 to identify RCTs reporting ISR or dermatologic outcomes for GLP‐1 RAs. Random‐effects meta‐analysis synthesised trial evidence. A retrospective disproportionality analysis of FAERS data evaluated all approved GLP‐1 RAs. Lower bound reporting odds ratios (LB ROR), proportional reporting ratios (PRR) and information components (IC) were calculated. Results The pooled meta‐analysis of 14 RCTs that reported ISRs (4861 patients; 396 ISR events) showed increased ISR risk with GLP‐1 RAs versus comparators (risk ratio 3.55; 95% confidence interval, 2.35–5.36; I 2 = 41.4%). Dermatologic events were infrequent and not significantly elevated. FAERS data analysis revealed potential ISR signals for exenatide and dulaglutide. Exenatide was associated with injection‐site haemorrhage (PRR: 27.6; LB ROR: 29.4; IC 025 : 4.6). Dulaglutide showed disproportionate reporting for injection‐site haemorrhage (PRR: 11.5; LB ROR: 11.5; IC 025 : 3.4). Conclusions GLP‐1 RAs are consistently linked to higher ISR risk, especially with exenatide and dulaglutide, while generalised dermatologic events are rare. Clinicians should counsel patients about ISR risk to support adherence and optimise outcomes.