Patient Allergic to Liraglutide Successfully Switched to Semaglutide Without Reaction

What the researchers found

A 56-year-old female patient with class 3 obesity developed well-defined, round, erythematous pruriginous (itchy) plaques surrounding the injection site approximately 24 hours after each liraglutide (Saxenda) administration, beginning one month after starting treatment.

The delayed-type hypersensitivity reaction was confirmed through allergy testing and histopathological examination of the skin lesions. Despite this reaction to liraglutide, the patient tolerated semaglutide without hypersensitivity, indicating that the allergenic component was specific to liraglutide rather than common to all GLP-1 receptor agonists.

Why it matters

As GLP-1 receptor agonists are prescribed to millions of people for diabetes and obesity, allergic reactions — though uncommon — will inevitably occur. Clinicians need to know whether a patient allergic to one GLP-1 drug must avoid the entire class or can safely switch to an alternative. This case provides evidence that switching within the class is possible, which is clinically important given the transformative benefits of GLP-1 therapy.

How the study worked

This is a clinical case report. The diagnosis was established through clinical presentation (delayed erythematous plaques at injection sites), allergy testing (to confirm liraglutide as the causative agent), and histopathological study of the affected skin. The patient was subsequently transitioned to semaglutide to assess cross-reactivity.

What this study cannot tell us

This is a single case report, so the finding of semaglutide tolerance in a liraglutide-allergic patient cannot be generalized to all patients. Delayed-type hypersensitivity reactions can vary in severity and mechanism between individuals. The specific component of liraglutide causing the reaction (the peptide backbone, fatty acid chain, or excipients) was not definitively identified. Long-term tolerance to semaglutide was not assessed.

How to read the evidence

This is a single case report — the lowest level of clinical evidence. While the diagnosis was rigorously confirmed with allergy testing and histopathology, the finding applies to only one patient. Case reports are valuable for identifying new clinical phenomena but cannot establish general treatment recommendations.

When this study was published

Published in 2024, this case report is timely given the massive increase in GLP-1 receptor agonist prescriptions for obesity in recent years, which has brought more attention to adverse drug reactions in this class.

The bigger picture

While liraglutide and semaglutide are both GLP-1 receptor agonists, they have different molecular structures — semaglutide has modifications that give it a longer half-life and different pharmacological profile. This structural difference likely explains why the patient tolerated semaglutide despite reacting to liraglutide. As more GLP-1 drugs enter the market (tirzepatide, survodutide, etc.), understanding cross-reactivity patterns will become increasingly important for allergy management.

Questions still open

• Is the allergenic component in liraglutide the peptide itself, the fatty acid modification, or an excipient in the formulation?
• What is the actual cross-reactivity rate between different GLP-1 receptor agonists in patients with confirmed hypersensitivity?
• Should allergy testing for the alternative GLP-1 drug be performed before switching, or is empirical trial sufficient?

Common questions

Read the original research

Delayed Type Hypersensitivity Reaction Induced By Liraglutide With Tolerance to Semaglutide.

JCEM case reports, 2(6), luae105

Citation

Moreno-Borque, Ricardo; Guhl-Millán, Guillermo; Mera-Carreiro, Sara; Pazos-Guerra, Mario; Cortés-Toro, Jose Antonio; López-Bran, Eduardo. (2024). Delayed Type Hypersensitivity Reaction Induced By Liraglutide With Tolerance to Semaglutide.. JCEM case reports, 2(6), luae105. https://doi.org/10.1210/jcemcr/luae105