Glucagon-like Peptide-1 Receptor Agonist-Associated Injection Site and Dermatologic Reactions.
Exenatide has the highest reported rate of skin and injection-site reactions among GLP-1 receptor agonists, with 53.1% of reports indicating such issues.
Where it sits
this study against the rest of the exenatide corpusSummary and findings
This study reviewed the prevalence and clinical features of injection site and dermatologic reactions associated with glucagon-like peptide-1 receptor agonists, including exenatide. Among 442,567 adverse event reports, 137,412 (31.0%) involved skin and injection-site reactions. Exenatide had the highest proportion of these reports at 53.1%.
Abstract
<h4>Background</h4>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.<h4>Objective</h4>To review the prevalence, clinical features, mechanisms, and management of non-immunologic Injection Site and Dermatologic Reactions associated with GLP-1RAs.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
Background
This paper addresses the clinical question of the prevalence and characteristics of cutaneous adverse events associated with GLP-1 receptor agonists, which are increasingly used for type 2 diabetes and obesity. Prior knowledge indicated that gastrointestinal side effects were the most common, but cutaneous reactions may also significantly impact patient experience. Understanding these reactions is crucial for improving patient management and outcomes.
Methods
The study conducted a review of clinical trials, pharmacovigilance studies, and case reports related to GLP-1RAs. It extracted adverse event reports from the FAERS database, focusing on injection-site and dermatologic reactions. The analysis included a total of 442,567 reports, with a specific emphasis on the rates of skin and injection-site reactions across various GLP-1RAs.
Results
Among the 442,567 FAERS reports, 137,412 (31.0%) involved skin and injection-site reactions. Exenatide had the highest proportion of these reports at 53.1%, followed by dulaglutide at 33.5% and tirzepatide at 32.6%. The most common reactions included pain, bleeding, erythema, bruising, mass, pruritus, and swelling. Most reactions were mild to moderate and did not require treatment discontinuation.
Interpretation
The findings indicate that cutaneous adverse events are a significant concern with GLP-1RAs, particularly with exenatide. While the statistical significance of the findings is clear, the clinical significance may vary based on the severity and management of these reactions. Limitations include reliance on voluntary reporting, which may not fully represent the incidence of these reactions in the general population.
Key findings
- 137,412 (31.0%) of reports involved skin and injection-site reactions.
- Exenatide demonstrated the highest proportion of skin and injection-site reports at 53.1%.
- Dulaglutide had 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.
- Most reactions were mild to moderate and generally managed symptomatically.
Limitations
- Relies on voluntary adverse event reporting, which may not capture all reactions.
- Potential reporting bias in the FAERS data.
- No prospective studies were conducted to confirm findings.
- Short follow-up period may not reflect long-term outcomes.