What are the signs of an allergic reaction to semaglutide?

October 9, 2025 •

4 min read

Although serious allergic reactions to semaglutide, such as anaphylaxis and angioedema, are rare, they are a possible risk for users of this medication. It is crucial for patients prescribed semaglutide (available under brand names like Ozempic and Wegovy) to understand what are the signs of an allergic reaction to semaglutide so they can take appropriate action.

Quick Summary

Allergic reactions to semaglutide can range from mild, localized injection site issues to severe, systemic symptoms like facial swelling and breathing problems. Severe reactions require immediate medical attention.

Key Points

Differentiate Symptoms: Distinguish between common, mild injection site irritation and a severe systemic allergic reaction.
Recognize Severe Signs: Severe allergic reaction symptoms include swelling of the face, lips, tongue, or throat; difficulty breathing; and widespread hives.
Seek Immediate Help: Call 911 or your local emergency services immediately if you experience severe symptoms like swelling or trouble breathing.
Manage Mild Reactions: Minor injection site redness or itching can often be soothed with a cold compress or over-the-counter creams, but you should still inform your doctor.
Discontinue Use: Stop taking semaglutide immediately if you suspect a serious allergic reaction and seek guidance from a medical professional.
Understand Risk Factors: Those with a history of allergic reactions to other GLP-1 agonists should exercise caution, as cross-reactivity is possible.

Understanding Allergic Reactions to Semaglutide

Semaglutide is a medication widely used for managing type 2 diabetes and assisting with chronic weight management. It belongs to a class of drugs called GLP-1 receptor agonists. While many of its common side effects are gastrointestinal (such as nausea, vomiting, and diarrhea), it's important for patients to be aware of the signs of an allergic or hypersensitivity reaction.

Allergic reactions occur when the immune system mistakenly identifies the drug as a threat and launches an attack. These reactions can manifest differently for each individual and can vary in severity, from minor and localized to severe and systemic, requiring immediate emergency medical care.

Differentiating Mild vs. Severe Allergic Symptoms

It is important to recognize the difference between a minor injection site reaction and a true allergic response. A minor reaction is often a temporary immune response to the physical injection or the medication itself, whereas a systemic allergic reaction (hypersensitivity) can affect multiple bodily systems and is far more serious.

Mild Injection Site Reactions

These reactions are typically localized, minor, and self-limiting, often resolving on their own within a day or two.

Redness: Mild redness around the area where the injection was given.
Itching: A localized itching sensation at the injection site.
Swelling: Slight swelling or a small, soft lump at the site.
Rash: A mild, non-spreading rash or hives that are confined to the area of injection.

Severe Allergic Reactions (Anaphylaxis and Angioedema)

Serious allergic reactions to semaglutide, though rare, can be life-threatening and require immediate medical attention. Symptoms can occur within minutes to hours after administration and include:

Swelling of the Face and Airways: This is a key sign of a serious reaction, known as angioedema. It involves large, hive-like swelling of the face, eyelids, lips, tongue, or throat.
Breathing Problems: Shortness of breath, wheezing, hoarseness, or difficulty breathing and swallowing.
Severe Rash and Itching: A widespread rash or hives that covers a large area of the body and is often accompanied by severe itching.
Cardiovascular Symptoms: A very rapid heartbeat, dizziness, or feeling like you might faint.
Systemic Symptoms: A general feeling of being unwell, sweating, or a drop in blood pressure.

Comparison of Injection Site vs. Systemic Allergic Reactions


Symptom Type	Injection Site Reaction	Severe Systemic Allergic Reaction	Action Required
Appearance	Mild redness, swelling, or rash localized to the injection site.	Widespread rash or large, hive-like swelling of the face, lips, or tongue.	Immediate medical help for severe reactions.
Sensation	Mild itching or burning at the injection spot.	Intense itching, dizziness, or fainting.	Contact a healthcare provider for mild issues.
Respiratory	None.	Difficulty breathing, swallowing, or wheezing.	Immediate medical help for severe reactions.
Onset	Often occurs within hours of injection.	Can occur within minutes to hours after injection.	Stop medication and call 911 for severe reactions.

What to Do If You Suspect an Allergic Reaction

If you experience any signs of a severe allergic reaction to semaglutide, it is critical to seek emergency medical help immediately.

Stop Using the Medication: Do not administer any further doses of semaglutide.
Call 911 (or your local emergency number): If you experience swelling of the face, lips, or tongue, or have trouble breathing, call for emergency medical assistance.
Contact Your Healthcare Provider: For less severe reactions, such as a rash confined to the injection site, contact your healthcare provider for guidance on managing symptoms and determining if a different treatment is necessary.
Manage Mild Symptoms: For minor injection site reactions, a cold compress and over-the-counter antihistamines or hydrocortisone cream may provide relief.

The Science Behind Semaglutide Hypersensitivity

Allergic reactions to semaglutide are classified as hypersensitivity reactions. In some cases, the immune system responds to the drug's peptide structure, potentially triggering histamine release and inflammation. While the incidence of anaphylaxis with semaglutide is low, studies on this class of drugs (GLP-1 receptor agonists) have found that serious hypersensitivity reactions can occur.

For patients with a history of anaphylaxis or angioedema related to other GLP-1 receptor agonists, caution is advised when considering semaglutide. The FDA label for Wegovy, a semaglutide product, warns against its use in patients with a prior serious hypersensitivity reaction to semaglutide or its components.

Conclusion

Recognizing the distinction between a common injection site reaction and a severe systemic allergic reaction is vital for anyone taking semaglutide. While mild irritation at the injection site is generally not a cause for concern and can be managed at home, symptoms like swelling of the face, lips, tongue, or difficulty breathing are a medical emergency. It is always best to consult your healthcare provider regarding any new or concerning symptoms to ensure your safety and determine the best course of action. For more information on the risks associated with this medication, refer to the Food and Drug Administration (FDA) label for WEGOVY.

Frequently Asked Questions

An injection site reaction is typically localized to the area of the injection, causing mild redness, swelling, or itching that subsides within a day or two. A true allergic reaction, or hypersensitivity, is a systemic response affecting multiple body parts, with more severe symptoms like swelling of the face, lips, or throat, and difficulty breathing.

While reactions can occur at any time, immediate hypersensitivity reactions can begin within minutes to hours after injection. One case study noted angioedema and anaphylaxis occurring hours to days after administration.

If the rash is mild and localized to the injection site, you can manage it with a cool compress and avoid scratching. However, if the rash is widespread, severe, or accompanied by other symptoms like swelling or breathing difficulty, seek immediate medical attention.

Yes, steps can be taken to minimize injection site reactions. These include rotating your injection sites, allowing the alcohol swab to dry completely, ensuring proper injection technique, and not rubbing the area afterward.

No, severe allergic reactions like anaphylaxis are considered rare with semaglutide. However, due to the life-threatening nature of anaphylaxis, it is important to be aware of the signs.

The FDA label for Wegovy advises caution in patients with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist, as it is unknown if these patients will be predisposed to reactions with semaglutide. Always inform your healthcare provider of any prior medication allergies.

Swelling of the mouth, throat, lips, or tongue is a sign of a serious allergic reaction (angioedema). This is a medical emergency. You should stop the medication immediately and get emergency medical help.