Many people with type 2 diabetes prescribed Trulicity (dulaglutide) wonder whether this medication might increase their risk of blood clots. Trulicity is a glucagon-like peptide-1 (GLP-1) receptor agonist used to improve blood glucose control in adults with type 2 diabetes. Whilst all medications carry potential side effects, understanding the evidence around Trulicity and thrombotic risk is important for informed decision-making. This article examines the clinical evidence, recognised side effects, and cardiovascular safety profile of Trulicity, helping patients and healthcare professionals understand whether blood clots are an established concern with this widely prescribed diabetes medication.

What Is Trulicity and How Does It Work?

Trulicity (dulaglutide) is a prescription medicine licensed in the UK for the treatment of type 2 diabetes mellitus in adults. It belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists, which work by mimicking the action of a naturally occurring hormone that helps regulate blood glucose levels.

The mechanism of action involves several complementary pathways. Trulicity stimulates insulin secretion from pancreatic beta cells in a glucose-dependent manner, meaning it only promotes insulin release when blood sugar levels are elevated. This reduces the risk of hypoglycaemia compared to some other diabetes medications. Additionally, it suppresses the release of glucagon (a hormone that raises blood glucose) and slows gastric emptying, which helps moderate the rise in blood sugar after meals. Many patients also experience modest weight loss, which can be beneficial for overall metabolic health.

Trulicity is administered as a once-weekly subcutaneous injection using a pre-filled pen device. It is available in four strengths (0.75 mg, 1.5 mg, 3.0 mg and 4.5 mg) and is typically injected into the abdomen, thigh or upper arm on the same day each week. According to the Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), Trulicity is indicated either as monotherapy when metformin is inappropriate, or in combination with other glucose-lowering medicines including insulin.

Importantly, Trulicity is not for use in people with type 1 diabetes or diabetic ketoacidosis and is not a substitute for insulin. The National Institute for Health and Care Excellence (NICE) guidance (NG28) recommends GLP-1 receptor agonists like Trulicity for patients who have not achieved adequate glycaemic control with existing therapies and meet specific criteria, including a BMI of 35 kg/m² or above (adjusted for ethnicity) or where weight loss would benefit other significant obesity-related comorbidities. Treatment should be continued only if there is a reduction of at least 11 mmol/mol (1%) in HbA1c and a weight loss of at least 3% at 6 months.

Recognised Side Effects of Trulicity in the UK

Like all medicines, Trulicity can cause side effects, although not everyone experiences them. The most commonly reported adverse effects are gastrointestinal in nature, affecting the digestive system. These include:

• Nausea (very common, affecting more than 1 in 10 people)

• Diarrhoea and vomiting (common)

• Abdominal pain and decreased appetite

• Dyspepsia (indigestion) and constipation

These gastrointestinal symptoms are typically most pronounced when starting treatment or increasing the dose, and often diminish over time as the body adjusts to the medication. Patients are generally advised to start with smaller meals and avoid high-fat foods during the initial weeks of therapy.

Other recognised side effects documented in the UK Summary of Product Characteristics include hypoglycaemia (particularly when used in combination with insulin or sulfonylureas), injection site reactions, fatigue, and a small average increase in heart rate that is rarely clinically significant. More serious adverse effects include:

• Acute pancreatitis (inflammation of the pancreas) – if suspected, Trulicity should be discontinued immediately and urgent medical assessment sought

• Gallbladder disease including cholelithiasis (gallstones) and cholecystitis (gallbladder inflammation)

• Dehydration and acute kidney injury – persistent vomiting or diarrhoea can lead to dehydration and kidney problems

Regarding blood clots specifically, there is no established link between Trulicity and an increased risk of thrombotic events (blood clots) in the official prescribing information approved by the MHRA or EMA. Blood clots are not listed among the known side effects in the patient information leaflet or the Summary of Product Characteristics. However, it is important to recognise that people with type 2 diabetes have an inherently elevated baseline risk of cardiovascular events, including thrombosis, due to the metabolic condition itself rather than the medication used to treat it.

If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in the package leaflet. You can also report side effects directly via the MHRA Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

Cardiovascular Safety and Clinical Evidence

Cardiovascular safety is a critical consideration for all diabetes medications, given that people with type 2 diabetes face substantially elevated risks of heart disease, stroke, and vascular complications. Trulicity has been extensively studied in this context, most notably in the REWIND trial (Researching Cardiovascular Events with a Weekly Incretin in Diabetes), a large-scale cardiovascular outcomes study.

The REWIND trial, published in The Lancet in 2019, enrolled over 9,900 participants with type 2 diabetes and followed them for a median of 5.4 years. The results demonstrated that Trulicity reduced the risk of major adverse cardiovascular events (MACE) — a composite endpoint including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke — by 12% compared to placebo. This cardiovascular benefit was observed across a broad population, including those with and without established cardiovascular disease.

Regarding thrombotic events specifically, the trial data showed no increased risk of blood clots associated with Trulicity use. The reduction in stroke events observed in the trial should not be interpreted as an antithrombotic effect, and Trulicity is not an antithrombotic therapy. It does not replace standard preventive measures for thrombosis in patients at risk. The mechanisms potentially contributing to cardiovascular benefits may include improvements in blood pressure, body weight, and possibly effects on inflammation and endothelial function, though these mechanisms remain under investigation.

NICE guidance (NG28) acknowledges the cardiovascular benefits of certain diabetes medications, with SGLT2 inhibitors often prioritised for patients with established cardiovascular disease, heart failure or chronic kidney disease. GLP-1 receptor agonists like Trulicity may be considered where appropriate, particularly for patients who would benefit from weight loss. The NHS approach increasingly recognises these medications as having potential dual benefits: improving glycaemic control whilst potentially offering cardiovascular risk reduction. For patients concerned about cardiovascular safety, the evidence suggests that Trulicity does not increase thrombotic risk compared to standard diabetes care.

When to Seek Medical Advice While Taking Trulicity

Whilst Trulicity is generally well-tolerated, certain symptoms warrant prompt medical attention. Patients should be aware of warning signs that require urgent assessment:

Call 999 or go to A&E immediately if you experience:

• Severe chest pain or pressure that may spread to arms, neck or jaw

• Sudden severe breathlessness or difficulty breathing

• Signs of stroke such as facial drooping, arm weakness, or speech difficulties

• Severe, persistent abdominal pain that may radiate to the back, potentially indicating pancreatitis

• Signs of a serious allergic reaction, including difficulty breathing, swelling of the face, lips, tongue or throat, or severe skin rash

Contact your GP urgently or call NHS 111 if you experience:

• Symptoms potentially related to blood clots, such as leg pain with swelling, warmth and redness (possible deep vein thrombosis)

• Right upper abdominal pain, fever or yellowing of the skin/eyes (possible gallbladder problems)

• Symptoms of dehydration from persistent vomiting or diarrhoea, such as dizziness, reduced urination, or extreme thirst

• Visual changes or eye pain, particularly if you have existing diabetic retinopathy or have recently started insulin alongside Trulicity

Contact your GP or diabetes specialist nurse if:

• Gastrointestinal side effects persist beyond the first few weeks or significantly impact quality of life

• You experience recurrent hypoglycaemia (blood glucose below 4 mmol/L)

• You develop unexplained symptoms or have concerns about your medication

• You are planning pregnancy or become pregnant

Trulicity is not recommended during pregnancy and should be discontinued at least one month before a planned pregnancy. If you become pregnant while taking Trulicity, contact your healthcare provider immediately. Discuss breastfeeding with your doctor if you are considering Trulicity after childbirth.

Regular diabetes reviews, typically conducted in primary care or specialist clinics, provide opportunities to discuss any concerns about Trulicity. NHS structured education programmes (such as DESMOND or X-PERT) and local diabetes services offer additional support for medication management and cardiovascular risk reduction strategies.

Frequently Asked Questions