GLP-1 agonists and lymphoproliferative disorders in adults represent an important clinical consideration as these diabetes and obesity medications become increasingly prescribed. GLP-1 agonists, such as semaglutide and liraglutide, work by mimicking a natural hormone to improve blood glucose control and promote weight loss. Lymphoproliferative disorders encompass a range of conditions involving abnormal lymphocyte proliferation, from benign to malignant, including non-Hodgkin lymphoma and chronic lymphocytic leukaemia. Whilst current evidence shows no established causal link between GLP-1 agonist use and these haematological conditions, individualised assessment remains essential for patients with existing lymphoproliferative disorders or those at risk.

What Are GLP-1 Agonists and Lymphoproliferative Disorders?

GLP-1 agonists (glucagon-like peptide-1 receptor agonists) are a class of medications primarily used to manage type 2 diabetes mellitus and, more recently, obesity. These drugs work by mimicking the action of the naturally occurring hormone GLP-1, which is released from the intestine in response to food intake. The mechanism of action includes stimulating insulin secretion in a glucose-dependent manner, suppressing glucagon release, slowing gastric emptying, and promoting satiety through central nervous system effects. Common examples include semaglutide (Ozempic, Wegovy, Rybelsus), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and exenatide (Byetta, Bydureon).

Lymphoproliferative disorders represent a heterogeneous group of conditions characterised by the abnormal proliferation of lymphocytes—the white blood cells that form a crucial part of the immune system. These disorders range from benign conditions to malignant cancers. The spectrum includes:

• Non-Hodgkin lymphoma (various subtypes including diffuse large B-cell lymphoma, follicular lymphoma)

• Hodgkin lymphoma

• Chronic lymphocytic leukaemia (CLL)

• Multiple myeloma

• Post-transplant lymphoproliferative disorder

These conditions can affect lymph nodes, bone marrow, spleen, and other organs. Symptoms may include painless lymph node enlargement, unexplained weight loss, night sweats, fever, and fatigue. The aetiology is multifactorial, involving genetic predisposition, immune dysfunction, viral infections (such as Epstein-Barr virus), and environmental factors. As GLP-1 agonists have become increasingly prescribed, questions have emerged regarding their safety profile in patients with existing lymphoproliferative disorders or those at risk of developing such conditions.

Current Evidence on GLP-1 Agonists and Cancer Risk

The relationship between GLP-1 agonists and cancer risk, including lymphoproliferative disorders, has been the subject of ongoing pharmacovigilance and clinical research. There is currently no established causal link between GLP-1 agonist use and the development of lymphoproliferative disorders in adults. Pre-marketing clinical trials and post-marketing surveillance data have not demonstrated a consistent signal suggesting these medications increase the risk of lymphoid malignancies.

Large-scale cardiovascular outcome trials, such as LEADER (liraglutide), SUSTAIN-6 (semaglutide), and REWIND (dulaglutide), included thousands of patients followed for several years. These studies did not reveal an increased incidence of haematological malignancies compared to placebo groups. Comprehensive meta-analyses examining cancer outcomes across multiple GLP-1 agonist trials have found no significant elevation in overall cancer risk, including haematological cancers.

The Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) continue to monitor the safety profile of GLP-1 agonists through routine pharmacovigilance. To date, neither regulatory body has issued warnings specifically linking these agents to lymphoproliferative disorders. However, as with all medications, ongoing surveillance remains essential, particularly as real-world use expands beyond the populations studied in clinical trials.

It is worth noting that product information for GLP-1 agonists mentions thyroid C-cell tumours observed in rodent studies, though the human relevance of this finding remains unknown. Additionally, the SUSTAIN-6 trial identified an increased risk of diabetic retinopathy complications with semaglutide in patients with pre-existing retinopathy, particularly with rapid HbA1c reduction.

It is important to note that patients with diabetes and obesity—the primary indications for GLP-1 agonists—may have baseline differences in cancer risk due to metabolic factors, chronic inflammation, and other comorbidities. Disentangling the effects of the medication from underlying disease characteristics requires careful epidemiological study. Current evidence suggests that the benefits of glycaemic control and weight reduction likely outweigh theoretical cancer concerns for most patients.

Safety Considerations for Adults with Lymphoproliferative Disorders

For adults with existing lymphoproliferative disorders, the decision to initiate or continue GLP-1 agonist therapy requires individualised clinical assessment. While there is no evidence that these medications adversely affect the course of lymphoid malignancies, several practical considerations merit attention.

Gastrointestinal adverse effects are among the most common side effects of GLP-1 agonists, including nausea, vomiting, diarrhoea, and reduced appetite. These effects typically diminish over time but can be particularly problematic in patients undergoing chemotherapy or immunotherapy for lymphoproliferative disorders, where gastrointestinal symptoms may already be present. The additive effect could compromise nutritional status and quality of life. Dose titration should be gradual, and antiemetic strategies may be required.

Weight loss, whilst often desirable in patients with type 2 diabetes or obesity, may be inappropriate in individuals with active malignancy who are at risk of cachexia. Unintentional weight loss is a poor prognostic indicator in cancer patients. Healthcare professionals should carefully monitor body weight and nutritional parameters, with dietitian and oncology team involvement in treatment planning.

Drug interactions are generally minimal with injectable GLP-1 agonists, as they are not metabolised by cytochrome P450 enzymes. The delayed gastric emptying effect may theoretically alter the absorption of oral medications with narrow therapeutic indices. For oral semaglutide (Rybelsus), specific administration instructions must be followed (taken on an empty stomach with a small amount of water, waiting 30 minutes before food or other medications) to ensure proper absorption.

Immune function is not directly suppressed by GLP-1 agonists, which is reassuring for patients with lymphoproliferative disorders who may already have compromised immunity. Unlike corticosteroids or immunosuppressive agents, these medications do not appear to increase infection risk significantly, though patients should remain vigilant for signs of infection.

Additional safety considerations include:

• Hypoglycaemia risk when GLP-1 agonists are used with insulin or sulfonylureas; dose reductions of these medications may be needed

• Pancreatitis risk – patients should be informed about symptoms (severe abdominal pain) requiring urgent medical attention

• Gallbladder disease – increased risk of gallstones with weight loss

• Acute kidney injury – possible risk with severe dehydration from gastrointestinal side effects

• Diabetic retinopathy – particularly with semaglutide in patients with pre-existing retinopathy

Monitoring and Clinical Guidance for GLP-1 Agonist Use

NICE guidance on the management of type 2 diabetes (NG28) and obesity (CG189, TA875 for semaglutide, TA664 for liraglutide) provides a framework for GLP-1 agonist use but does not specifically address patients with lymphoproliferative disorders. Clinical decision-making should therefore integrate general prescribing principles with haematology-oncology considerations.

Baseline assessment before initiating GLP-1 agonist therapy should include:

• Full blood count to establish baseline haematological parameters

• Renal and hepatic function tests (note: exenatide is not recommended if eGFR <30 mL/min/1.73 m²)

• Assessment of gastrointestinal symptoms and nutritional status

• Review of concurrent medications and potential interactions

• Diabetic retinopathy screening in patients with diabetes, particularly before starting semaglutide

• Discussion of treatment goals balancing glycaemic control, weight management, and cancer-related considerations

Ongoing monitoring should be more frequent in patients with lymphoproliferative disorders. This includes:

• Regular weight checks (monthly initially) to detect excessive or unintended weight loss

• HbA1c monitoring every 3–6 months to assess glycaemic efficacy

• Renal function monitoring, particularly during episodes of dehydration from gastrointestinal side effects

• Gastrointestinal symptom assessment at each review

• Retinopathy monitoring in patients with pre-existing diabetic retinopathy

• Coordination with haematology-oncology teams to ensure integrated care

Dose titration should follow manufacturer guidance but may require slower escalation in patients experiencing treatment-related side effects from their lymphoproliferative disorder management. If gastrointestinal adverse effects are intolerable, consider switching to an alternative GLP-1 agonist, as tolerability profiles vary between agents.

For oral semaglutide, ensure patients understand the specific administration requirements (taking on an empty stomach with a small amount of water, waiting 30 minutes before food or other medications).

If using with insulin or sulfonylureas, consider reducing doses of these medications to minimise hypoglycaemia risk.

Discontinuation should be considered if the patient develops severe gastrointestinal symptoms, significant unintended weight loss (>5% body weight over 3 months should trigger reassessment), or if the medication interferes with cancer treatment adherence. The decision should involve multidisciplinary discussion.

When to Discuss GLP-1 Therapy with Your Healthcare Team

Open communication with your healthcare team is essential when considering or using GLP-1 agonist therapy, particularly if you have a history of lymphoproliferative disorders. You should initiate a discussion if:

• You are newly diagnosed with a lymphoproliferative disorder whilst taking a GLP-1 agonist

• You experience new or worsening symptoms such as unexplained lymph node swelling, persistent fever, drenching night sweats, or unintentional weight loss exceeding that expected from the medication

• Gastrointestinal side effects become severe or persistent, affecting your ability to eat, maintain hydration, or take other essential medications

• You are due to start chemotherapy or immunotherapy and need to discuss whether to continue, pause, or stop your GLP-1 agonist

• Your weight loss is excessive or you are concerned about nutritional status

• You experience symptoms of hypoglycaemia (sweating, shakiness, confusion) if taking insulin or sulfonylureas alongside a GLP-1 agonist

Before starting GLP-1 therapy, ensure your GP or diabetes specialist is aware of your complete medical history, including any current or previous lymphoproliferative disorder, even if in remission. This information allows for appropriate risk-benefit assessment and monitoring planning.

Red flag symptoms requiring urgent medical attention include:

• Severe, persistent abdominal pain (potential pancreatitis) – contact your GP urgently, call NHS 111, or attend A&E if severe

• Signs of dehydration from vomiting or diarrhoea – contact your GP or NHS 111 promptly

• Rapidly enlarging lymph nodes – contact your GP or haematology team urgently

• Unexplained bruising or bleeding – contact your GP or haematology team urgently

• Severe fatigue or breathlessness – seek urgent medical advice via GP, NHS 111, or A&E if severe

• Sudden changes in vision – seek urgent medical attention, particularly if you have diabetes with pre-existing retinopathy

Shared decision-making is paramount. Your healthcare team should explain the potential benefits of improved glycaemic control and weight management against any theoretical or practical concerns. For most patients with stable or treated lymphoproliferative disorders, GLP-1 agonists can be used safely with appropriate monitoring. However, individual circumstances vary, and treatment plans should be personalised to your specific situation, treatment phase, and overall health goals.

If you experience any suspected side effects from your medication, report them to the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk).

Frequently Asked Questions