Glucagon-like Peptide-1 Receptor Agonist-Associated Injection Site and Dermatologic Reactions

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity, with expanding therapeutic applications. Although gastrointestinal adverse events are the most recognized toxicities, Cutaneous adverse events constitute a large burden of total adverse reactions.

To review the prevalence, clinical features, mechanisms, and management of non-immunologic Injection Site and Dermatologic Reactions associated with GLP-1RAs.

A review of clinical trials, pharmacovigilance studies, and case reports and series was performed. In addition, adverse event reports for tirzepatide, semaglutide, liraglutide, exenatide, dulaglutide, and lixisenatide were extracted from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Injection-site events were combined with skin-related adverse events to generate an adjusted "Skin and Injection-Site Reactions" category for comparison across agents.

Among 442,567 FAERS reports, 137,412 (31.0%) involved skin and injection-site reactions, representing the third most frequently reported adverse event category. Exenatide demonstrated the highest proportion of skin and injection-site reports (53.1%), followed by dulaglutide (33.5%), tirzepatide (32.6%), liraglutide (17.1%), semaglutide (12.2%), and lixisenatide (6.9%). Common reactions included pain, bleeding, erythema, bruising, mass, pruritus, and swelling. Additional adverse events included dysesthesias, nodules, granulomatous reactions, bruising, and hyperhidrosis. Most reactions were mild to moderate and generally managed symptomatically without requiring treatment discontinuation.

Non-immunologic cutaneous adverse events comprise a substantial proportion of reported GLP-1RA-associated adverse events with differing rates among individual agents. Recognition of these reactions and appropriate supportive management may improve patient outcomes. Prospective studies are needed to better define their adverse event risk rates, mechanisms, and optimal management strategies.