Glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide, dulaglutide, and liraglutide are increasingly prescribed in the UK for type 2 diabetes and weight management. Whilst these medications have a well-established safety profile, patients occasionally report concerns about swollen lymph nodes during treatment. It is important to understand that lymphadenopathy is not a recognised adverse effect of GLP-1 medications according to UK regulatory data. Swollen lymph nodes occurring during GLP-1 therapy typically have alternative causes requiring appropriate clinical evaluation. This article examines the relationship between GLP-1 medications and lymphadenopathy, identifies common causes of swollen lymph nodes, and provides guidance on when to seek medical advice.

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

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications primarily prescribed for the management of type 2 diabetes mellitus and, more recently, for weight management in adults with obesity or overweight with weight-related comorbidities. In the UK, GLP-1 medications include semaglutide (Ozempic, Wegovy, Rybelsus), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and exenatide (Byetta, Bydureon).

These medications work by mimicking the action of naturally occurring GLP-1, a hormone released by the intestine in response to food intake. GLP-1 receptor agonists enhance glucose-dependent insulin secretion from pancreatic beta cells, suppress inappropriate glucagon release, slow gastric emptying, and promote satiety through central nervous system pathways. This multifaceted mechanism helps improve glycaemic control in people with type 2 diabetes whilst also facilitating weight loss.

Most GLP-1 medications are administered via subcutaneous injection, either daily or weekly depending on the specific formulation, though oral semaglutide (Rybelsus) is available for type 2 diabetes. According to NICE guideline NG28, GLP-1 receptor agonists may be considered for type 2 diabetes when metformin is contraindicated or not tolerated, or in combination with other diabetes medications. Specific criteria include a BMI ≥30 kg/m² (adjusted for ethnicity), or weight-related complications and BMI <30 kg/m². For obesity management, NICE technology appraisal TA875 recommends semaglutide (Wegovy) only within specialist weight management services, for people with a BMI of at least 35 kg/m² (or 30 kg/m² with weight-related comorbidities) and as part of a programme including diet and physical activity for a maximum of 2 years.

Whilst GLP-1 medications are generally well-tolerated, patients may experience various side effects. Understanding the pharmacological profile of these drugs helps contextualise any symptoms that arise during treatment, including concerns about swollen lymph nodes, which warrant careful clinical evaluation to determine their underlying cause.

Common Causes of Swollen Lymph Nodes While Taking GLP-1 Drugs

Swollen lymph nodes (lymphadenopathy) can occur for numerous reasons, and it is important to recognise that lymphadenopathy is not listed as an adverse reaction in the UK Summaries of Product Characteristics (SmPCs) for GLP-1 receptor agonists. When patients taking GLP-1 medications notice swollen lymph nodes, the cause is typically unrelated to the medication itself.

Common causes of lymphadenopathy that may coincidentally occur during GLP-1 treatment include:

• Viral or bacterial infections: Upper respiratory tract infections, pharyngitis, dental infections, and other common illnesses frequently cause reactive lymph node enlargement, particularly in the neck, jaw, or armpit regions

• Localised skin infections or inflammation: Cellulitis, abscesses, or infected wounds near lymph node chains can trigger regional lymphadenopathy

• Systemic infections: Conditions such as infectious mononucleosis (glandular fever), cytomegalovirus, or toxoplasmosis may present with generalised lymph node swelling

• Immune-mediated conditions: Rheumatoid arthritis, lupus, and other autoimmune disorders can cause lymphadenopathy

• Malignancy: Lymphomas, leukaemias, or metastatic cancer may present with persistent or progressive lymph node enlargement

• Recent vaccination: Transient lymph node enlargement in the region draining the vaccination site is a common benign reaction

It is worth noting that injection site reactions are recognised side effects of GLP-1 medications, typically manifesting as localised redness, swelling, or discomfort at the injection site rather than distant lymph node enlargement. However, if an injection site becomes infected (showing increasing redness, warmth, pain, pus formation, or fever), regional lymph nodes may respond by enlarging as part of the normal immune response.

Patients with type 2 diabetes or obesity may have additional risk factors for infections or other conditions that cause lymphadenopathy, making it essential to evaluate swollen lymph nodes thoroughly rather than automatically attributing them to GLP-1 therapy. A comprehensive clinical assessment is necessary to identify the true underlying cause.

When to Seek Medical Advice About Swollen Lymph Nodes

Whilst many cases of lymphadenopathy resolve spontaneously as minor infections clear, certain features warrant prompt medical evaluation. Patients taking GLP-1 medications who notice swollen lymph nodes should contact their GP or healthcare provider if they experience any of the following:

Red flag features requiring urgent assessment:

• Persistent enlargement: Unexplained neck lumps persisting for ≥3 weeks (as per NICE guideline NG12 on suspected cancer recognition); other lymphadenopathy persisting for 4-6 weeks

• Progressive growth: Nodes that continue to increase in size over time

• Hard, fixed, or irregular nodes: Lymph nodes that feel firm, immobile, or have an irregular texture may indicate serious pathology

• Generalised lymphadenopathy: Swelling in multiple lymph node regions (neck, armpits, groin) simultaneously

• Systemic symptoms: Unexplained fever, drenching night sweats, unintentional weight loss (beyond expected GLP-1-related weight reduction), or persistent fatigue

• Associated symptoms: Difficulty swallowing, breathing difficulties, or hoarseness accompanying neck lymphadenopathy

According to NICE guideline NG12, lymphadenopathy with concerning features should prompt consideration of a suspected cancer pathway referral (2-week wait). Your GP will perform a thorough clinical examination, take a detailed history, and may arrange blood tests including full blood count, inflammatory markers (CRP, ESR), LDH, and specific infection screens as clinically indicated.

Additional investigations may include ultrasound imaging of the affected lymph nodes, chest X-ray, or referral for fine-needle aspiration or biopsy if malignancy or other serious pathology is suspected. It is important not to delay seeking medical advice if you have concerns, as early diagnosis significantly improves outcomes for serious conditions.

For patients continuing GLP-1 therapy, your healthcare provider will assess whether the medication should be continued during investigation of lymphadenopathy. In most cases, there is no reason to discontinue GLP-1 treatment unless another specific medical indication arises.

Managing Side Effects of GLP-1 Treatment in the UK

Whilst swollen lymph nodes are not a recognised side effect of GLP-1 medications, these drugs do have a well-characterised adverse effect profile that patients and healthcare professionals should monitor. Understanding and managing these effects optimises treatment adherence and outcomes.

Common gastrointestinal side effects are the most frequently reported issues with GLP-1 therapy:

• Nausea and vomiting: Typically most pronounced during treatment initiation or dose escalation; usually improves over several weeks

• Diarrhoea or constipation: Altered bowel habits due to delayed gastric emptying

• Abdominal discomfort: Bloating, dyspepsia, or gastro-oesophageal reflux symptoms

Practical management strategies recommended by NICE and specialist diabetes services include:

• Starting at the lowest licensed dose and titrating gradually according to the product's summary of product characteristics

• Eating smaller, more frequent meals and avoiding high-fat foods

• Maintaining adequate hydration, particularly if experiencing vomiting or diarrhoea

• Taking the injection at a consistent time as specified in the SmPC for your particular medication

Less common but important adverse effects include:

• Injection site reactions: Rotate injection sites systematically between abdomen, thigh, and upper arm to minimise localised reactions

• Hypoglycaemia: Risk increases when GLP-1 agents are combined with insulin or sulphonylureas; dose adjustments of these medications may be needed in consultation with your diabetes team

• Acute pancreatitis: If you develop severe, persistent abdominal pain radiating to the back, stop taking the medication and seek immediate medical attention

• Gallbladder disease: Rapid weight loss may increase risk of gallstones; report symptoms such as right upper abdominal pain, nausea, or vomiting

• Diabetic retinopathy complications: Particularly with semaglutide, rapid improvement in blood glucose can temporarily worsen existing retinopathy; attend regular eye screening

• Dehydration and acute kidney injury: Maintain adequate fluid intake, especially if experiencing gastrointestinal side effects

If you experience any suspected side effects, report them through the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk). Always discuss troublesome side effects with your GP or diabetes specialist nurse rather than discontinuing treatment abruptly. Alternative GLP-1 formulations, dose adjustments, or additional supportive medications may improve tolerability whilst maintaining the metabolic benefits of therapy.

Frequently Asked Questions