GLP-1 agonists, including semaglutide, dulaglutide, and liraglutide, are widely prescribed for type 2 diabetes and weight management. Whilst generally well-tolerated, allergic reactions to GLP-1 agonists can occur, ranging from mild injection site responses to rare but serious anaphylaxis. Recognising symptoms early—such as localised redness, widespread hives, or breathing difficulties—is essential for patient safety. This article explores how these reactions develop, who may be at risk, and what steps to take if symptoms arise. Understanding the difference between common side effects and true allergic responses helps ensure appropriate management and timely access to alternative treatments when needed.

What Are GLP-1 Agonists and How Do They Work?

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications primarily used to manage type 2 diabetes mellitus and, more recently, for weight management in specific patient groups. These medicines include injectable formulations such as semaglutide (Ozempic, Wegovy), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and exenatide (Byetta, Bydureon BCise), as well as oral semaglutide (Rybelsus). They work by mimicking the action of the naturally occurring GLP-1 hormone, which is released from the intestine in response to food intake.

The mechanism of action involves several complementary pathways. GLP-1 agonists bind to GLP-1 receptors on pancreatic beta cells, stimulating glucose-dependent insulin secretion—meaning insulin is released only when blood glucose levels are elevated. This reduces the risk of hypoglycaemia when used alone, though this risk increases when combined with sulfonylureas or insulin. Simultaneously, these agents suppress glucagon secretion from pancreatic alpha cells, further helping to lower blood glucose levels. They also slow gastric emptying, which prolongs the feeling of fullness and reduces post-meal glucose spikes.

Additionally, GLP-1 receptor agonists act on appetite centres in the brain, particularly the hypothalamus, leading to reduced food intake and promoting weight loss. This dual benefit—improved glycaemic control and weight reduction—has made them increasingly popular in clinical practice.

According to NICE guidance (NG28), GLP-1 agonists are recommended for type 2 diabetes when metformin and other treatments have not achieved adequate control. Specific criteria include a BMI of 35 kg/m² or above (or lower in certain ethnic groups), problems associated with high weight, or if insulin would otherwise be initiated but presents significant occupational implications. For weight management, NICE (TA875) recommends semaglutide 2.4 mg (Wegovy) only within specialist weight management services for adults with a BMI of at least 35 kg/m² (or 30 kg/m² with weight-related comorbidities) and as part of a supervised programme for a maximum of 2 years.

Whilst generally well-tolerated, like all medications, GLP-1 agonists can cause adverse effects, including gastrointestinal symptoms and, rarely, allergic reactions.

Recognising Allergic Reactions to GLP-1 Agonists

Allergic reactions to GLP-1 agonists are uncommon but can occur, and it is important for both patients and healthcare professionals to recognise them promptly. These reactions can range from mild hypersensitivity responses to severe, life-threatening anaphylaxis. According to product information, hypersensitivity reactions are classified as uncommon (affecting less than 1 in 100 people), while anaphylaxis is rare (affecting less than 1 in 1,000 people).

Allergic reactions typically occur due to an immune-mediated response to the drug molecule itself or to excipients (inactive ingredients) within the formulation. Some GLP-1 agonists are synthetic peptides that closely resemble human GLP-1, whilst others are modified versions designed to resist enzymatic breakdown and prolong duration of action. In rare cases, the body's immune system may recognise these molecules as foreign, triggering an allergic response.

Injection site reactions are the most frequently reported form of hypersensitivity with injectable GLP-1 agonists. These localised reactions may include redness, swelling, itching, or a rash at the site of injection. Whilst often mild and self-limiting, persistent or worsening injection site reactions warrant medical review, as they may indicate developing sensitivity to the medication.

More concerning are systemic allergic reactions, which affect the body more broadly. These can manifest as widespread urticaria (hives), angioedema (swelling of deeper skin layers, particularly around the face, lips, and throat), difficulty breathing, or cardiovascular symptoms such as dizziness and rapid heart rate. Anaphylaxis—a severe, rapid-onset allergic reaction—is rare but represents a medical emergency requiring immediate treatment with intramuscular adrenaline and calling 999 for an ambulance.

Patients should check the specific product information for details about excipients in their medication, as sensitivities to preservatives or other components may contribute to reactions in some individuals.

Common Symptoms and Warning Signs to Watch For

Understanding the spectrum of symptoms associated with allergic reactions to GLP-1 agonists enables early recognition and appropriate action. Symptoms can be categorised into local (injection site) and systemic manifestations, with varying degrees of severity.

Local injection site reactions are the most common and typically include:

• Erythema (redness) and warmth at the injection site

• Swelling or induration (hardening of tissue)

• Pruritus (itching) or discomfort

• Bruising or nodule formation in some cases (particularly with exenatide extended-release formulations, where nodules are common and often non-allergic)

These reactions usually appear within hours of injection and may resolve spontaneously within a few days. However, if symptoms persist beyond 72 hours, worsen progressively, or are accompanied by systemic features, medical advice should be sought.

Systemic allergic symptoms require more urgent attention and include:

• Cutaneous manifestations: widespread urticaria (raised, itchy welts), generalised pruritus, flushing, or angioedema affecting the face, lips, tongue, or throat

• Respiratory symptoms: shortness of breath, wheezing, throat tightness, or stridor (high-pitched breathing sound)

• Gastrointestinal symptoms: nausea, vomiting, abdominal cramping, or diarrhoea (though these can also be common non-allergic side effects of GLP-1 agonists)

• Cardiovascular symptoms: dizziness, light-headedness, rapid or weak pulse, or feeling faint

Anaphylaxis represents the most severe form of allergic reaction and is characterised by the rapid onset of symptoms affecting multiple organ systems. Warning signs include difficulty breathing, swelling of the tongue or throat, a sudden drop in blood pressure, loss of consciousness, and a sense of impending doom. Anaphylaxis typically develops within minutes to hours of drug administration and constitutes a medical emergency.

Patients should be advised to monitor for these symptoms after each dose of a GLP-1 agonist. While allergic reactions can occur at any time during treatment, they often develop after prior sensitisation, so vigilance should be maintained even after multiple uneventful doses.

What to Do If You Experience an Allergic Reaction

Prompt and appropriate action is essential when an allergic reaction to a GLP-1 agonist is suspected. The response depends on the severity and nature of symptoms.

For mild local injection site reactions:

• Apply a cold compress to the affected area to reduce swelling and discomfort

• Avoid rubbing or scratching the injection site

• Monitor the reaction over 24–48 hours for any worsening

• Contact your GP or diabetes specialist nurse if symptoms persist beyond 72 hours, spread beyond the injection site, or cause significant discomfort

• If symptoms are mild and self-limiting without systemic features, continue to monitor but discuss with your healthcare team before making any treatment changes

For moderate systemic reactions (such as widespread hives or mild facial swelling without breathing difficulty):

• Stop using the medication immediately and do not take further doses

• Contact your GP urgently or call NHS 111 for advice

• Take an oral antihistamine if available and previously tolerated (such as cetirizine or loratadine)

• Seek same-day medical assessment to determine whether the medication should be discontinued and to discuss alternative treatment options

For severe reactions or suspected anaphylaxis (difficulty breathing, throat swelling, collapse, or rapid symptom progression):

• Call 999 immediately and request an ambulance

• Use an adrenaline auto-injector if one has been prescribed and you have been trained in its use

• Lie flat with legs elevated (unless breathing is difficult, in which case sit upright)

• Do not attempt to drive yourself to hospital

• Inform paramedics and hospital staff about the GLP-1 agonist and timing of the last dose

Following any allergic reaction, it is important to report the event to your healthcare team. The reaction should be documented in your medical records, and you should be provided with clear guidance about avoiding the medication in future and identifying suitable alternatives.

Risk Factors and Who May Be More Susceptible

Whilst allergic reactions to GLP-1 agonists can occur in any patient, certain risk factors may increase susceptibility. Understanding these factors helps clinicians identify patients who may require closer monitoring when initiating treatment.

Previous allergic reactions to medications, particularly other injectable therapies or peptide-based drugs, represent the most significant risk factor. Patients with a documented history of drug allergies should inform their prescriber before starting a GLP-1 agonist. Cross-reactivity between different GLP-1 agonists is possible but not inevitable; however, caution is warranted if switching between agents following a reaction.

Atopic conditions—including asthma, eczema, allergic rhinitis, and food allergies—may predispose individuals to drug hypersensitivity reactions, though there is no official link establishing that atopic patients are definitively at higher risk for GLP-1 agonist allergies specifically. Nonetheless, these patients should be counselled about recognising allergic symptoms.

Excipient sensitivity is another consideration. GLP-1 agonist formulations contain various inactive ingredients, including preservatives, stabilisers, and solvents. Patients with known sensitivities to specific excipients should check the product information (SmPC) for their prescribed medication and discuss any concerns with their pharmacist or prescriber.

It is important to understand that immediate hypersensitivity reactions typically occur after prior sensitisation. This means reactions may appear after multiple doses rather than necessarily with first exposure, as the immune system requires time to develop a response to the medication.

It is important to note that gastrointestinal side effects—such as nausea, vomiting, and diarrhoea—are common pharmacological effects of GLP-1 agonists and do not represent allergic reactions. These symptoms typically improve with continued use and dose titration, whereas true allergic reactions tend to worsen with repeated exposure.

Alternative Treatments and Next Steps

If a patient experiences a confirmed allergic reaction to a GLP-1 agonist, discontinuation of the medication is necessary, and alternative treatment strategies must be considered. Fortunately, multiple therapeutic options exist for managing type 2 diabetes and obesity.

Alternative diabetes medications include several classes with different mechanisms of action:

• SGLT2 inhibitors (such as dapagliflozin, empagliflozin, or canagliflozin) work by increasing urinary glucose excretion and offer cardiovascular and renal benefits. NICE recommends these agents particularly for patients with established cardiovascular disease, heart failure, or chronic kidney disease.

• DPP-4 inhibitors (such as sitagliptin or linagliptin) enhance the body's own GLP-1 levels by preventing its breakdown, though they are less potent than GLP-1 agonists for glucose control and weight loss.

• Insulin therapy remains an effective option for patients requiring more intensive glycaemic control, though it may be associated with weight gain and hypoglycaemia risk.

• Thiazolidinediones (such as pioglitazone) improve insulin sensitivity but are used less frequently due to side effect profiles.

Switching between GLP-1 agonists may occasionally be considered if the reaction was mild and localised, as different formulations contain varying excipients. However, this should only be attempted under specialist supervision, with appropriate monitoring and emergency medication available. A formal allergy assessment by an immunologist or allergy specialist may be warranted in complex cases.

For weight management, if a GLP-1 agonist was prescribed primarily for obesity, alternatives include:

• Orlistat, a lipase inhibitor that reduces fat absorption

• Structured lifestyle interventions including dietary modification, increased physical activity, and behavioural therapy

• Bariatric surgery for patients meeting NICE criteria (typically BMI ≥40 kg/m² or ≥35 kg/m² with obesity-related conditions)

Next steps following an allergic reaction should include:

• Documentation of the allergy in medical records and prescription systems

• Provision of written information about the reaction for the patient

• Discussion of alternative treatment options tailored to individual clinical needs

• Regular follow-up to monitor diabetes control and adjust therapy as needed

• Consideration of referral to specialist services (endocrinology, allergy, or weight management) where appropriate

• Reporting the suspected adverse reaction to the MHRA via the Yellow Card Scheme (yellowcard.mhra.gov.uk)

Patients should be reassured that effective alternatives exist and that an allergic reaction to one medication does not preclude successful management of their condition with other therapies.

Frequently Asked Questions