Trulicity (dulaglutide) is a once-weekly injectable medication for type 2 diabetes that belongs to the GLP-1 receptor agonist class. Whilst it has relatively few serious drug interactions, certain medications—particularly insulin, sulphonylureas, and warfarin—require careful monitoring when used alongside Trulicity. Understanding which medicines may interact with Trulicity is essential for safe, effective diabetes management and avoiding complications such as hypoglycaemia or altered anticoagulation. This article examines the key medication interactions, provides guidance on combining Trulicity with other diabetes treatments, and explains when to seek professional medical advice about potential drug interactions.

What Is Trulicity and How Does It Work?

Trulicity (dulaglutide) is a once-weekly injectable medication used to manage type 2 diabetes mellitus in adults. It belongs to a class of drugs called 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. Trulicity is not indicated for type 1 diabetes or diabetic ketoacidosis.

The mechanism of action involves several complementary processes. 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 when used alone. Additionally, it suppresses the release of glucagon—a hormone that raises blood glucose—and slows gastric emptying, which helps moderate the post-meal rise in blood sugar.

Clinical trial evidence (the REWIND study) has shown cardiovascular benefits in patients with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, reducing the risk of major adverse cardiovascular events. The medication is administered via a pre-filled, single-dose pen injected subcutaneously once weekly, typically in the abdomen, thigh, or upper arm.

Common side effects include nausea, vomiting, diarrhoea, and decreased appetite, particularly during the initial weeks of treatment. These gastrointestinal effects often diminish over time as the body adjusts. Hypoglycaemia can occur when Trulicity is used in combination with insulin or sulphonylureas. More serious but rare adverse effects include pancreatitis and worsening of diabetic retinopathy (particularly in patients using insulin or with pre-existing retinopathy). Patients should be counselled about recognising symptoms of pancreatitis, such as severe abdominal pain, and instructed to seek immediate medical attention if these occur. Trulicity should be used with caution in patients with severe gastrointestinal disease.

Suspected adverse reactions should be reported via the MHRA Yellow Card Scheme at www.mhra.gov.uk/yellowcard or by searching for MHRA Yellow Card in the Google Play or Apple App Store.

Medications That May Interact with Trulicity

Trulicity does not have an extensive list of clinically significant drug interactions, but several medication classes warrant careful consideration and monitoring when used concurrently. Understanding these interactions is essential for optimising therapeutic outcomes and minimising adverse effects.

Medications that increase hypoglycaemia risk are the primary concern. Insulin secretagogues such as sulphonylureas (e.g., gliclazide, glimepiride) and meglitinides (e.g., repaglinide) stimulate insulin release independently of glucose levels. When combined with Trulicity, which also enhances insulin secretion, the cumulative effect may significantly increase the risk of low blood sugar. Dose reductions of the sulphonylurea may be necessary when initiating Trulicity to mitigate this risk.

Warfarin and other coumarin anticoagulants require monitoring. Post-marketing reports have documented increased International Normalised Ratio (INR) in patients taking warfarin concurrently with GLP-1 receptor agonists. The dulaglutide Summary of Product Characteristics (SmPC) advises more frequent INR monitoring when initiating or adjusting Trulicity in patients on warfarin or other coumarin derivatives. This precaution does not apply to direct oral anticoagulants (DOACs).

Other GLP-1 receptor agonists should not be used concurrently with Trulicity, as combining medicines from the same class offers no additional benefit and may increase adverse effects.

Whilst Trulicity slows gastric emptying, clinically significant effects on the absorption of most orally administered medications are not expected. However, patients taking any new medication should inform their healthcare provider that they are using Trulicity.

Insulin and Other Diabetes Medications with Trulicity

Trulicity is frequently prescribed alongside other glucose-lowering therapies as part of a comprehensive diabetes management strategy. Understanding how it interacts with these medications is crucial for safe and effective treatment.

Insulin therapy can be safely combined with Trulicity, and this combination is commonly used in clinical practice for patients requiring intensified glycaemic control. However, the concurrent use substantially increases hypoglycaemia risk. When initiating Trulicity in insulin-treated patients, consider reducing the basal insulin dose to mitigate this risk; dose adjustments should be individualised based on blood glucose monitoring and clinical response. Patients should be educated about hypoglycaemia symptoms—including tremor, sweating, confusion, and palpitations—and advised to monitor blood glucose more frequently during the adjustment period.

Sulphonylureas (e.g., gliclazide, glimepiride) may require dose reduction when Trulicity is initiated, as the combination increases the risk of hypoglycaemia. Dose adjustments should be made on an individual basis with careful blood glucose monitoring.

Metformin, the first-line oral agent for type 2 diabetes, has no significant interaction with Trulicity and the two are often prescribed together. Metformin's primary mechanism involves reducing hepatic glucose production and improving insulin sensitivity, complementing Trulicity's effects without increasing hypoglycaemia risk.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors such as dapagliflozin, empagliflozin, and canagliflozin can be used alongside Trulicity. This combination offers complementary mechanisms of glucose lowering and cardiovascular protection. However, patients should be monitored for volume depletion and educated about diabetic ketoacidosis (DKA) risk, particularly during intercurrent illness. The MHRA Drug Safety Update provides guidance on recognising and managing DKA risk with SGLT2 inhibitors, including the importance of sick-day rules (temporarily stopping the SGLT2 inhibitor during acute illness).

Thiazolidinediones (pioglitazone) may be used with Trulicity, though this combination is less common due to pioglitazone's side-effect profile, including fluid retention and weight gain—effects that may counteract some benefits of GLP-1 therapy. DPP-4 inhibitors (e.g., sitagliptin, linagliptin) should not be combined with Trulicity, as both work through the incretin pathway, offering little additional benefit whilst potentially increasing adverse effects.

Oral Medications: Timing and Absorption Considerations

Trulicity delays gastric emptying, but clinically significant effects on the absorption of most orally administered medications are not expected. Specific studies and the dulaglutide SmPC provide reassurance for commonly co-prescribed medicines.

Oral contraceptives have been studied specifically in relation to dulaglutide. Clinical pharmacology studies indicate that Trulicity does not significantly affect the overall exposure of ethinylestradiol and levonorgestrel, the components of most combined oral contraceptives. Contraceptive efficacy is maintained, and no routine adjustment in timing is required.

Levothyroxine, used for hypothyroidism management, should be taken on an empty stomach, typically 30–60 minutes before breakfast, as per standard guidance. No specific timing adjustment relative to Trulicity is routinely required. Thyroid function tests should be monitored if symptoms of hypothyroidism emerge or as clinically indicated.

Antibiotics can generally be taken as prescribed without specific timing adjustments relative to Trulicity. Clinically significant effects on antibiotic absorption are not expected. Patients should take antibiotics according to the prescriber's instructions and report any concerns about reduced therapeutic effect.

Paracetamol absorption studies have shown delayed time to maximum concentration but no significant change in overall exposure when taken with GLP-1 agonists. This suggests that whilst pain relief onset might be slightly delayed, the total analgesic effect remains unchanged. Patients can continue paracetamol as needed without specific timing restrictions.

Patients starting any new oral medication should inform their healthcare provider or pharmacist that they are taking Trulicity to allow for individualised advice.

When to Seek Medical Advice About Drug Interactions

Patients prescribed Trulicity should be empowered to recognise situations requiring professional medical guidance regarding potential drug interactions and medication management.

Before starting any new medication—whether prescription, over-the-counter, or herbal supplement—patients should inform their GP, pharmacist, or diabetes specialist nurse that they are taking Trulicity. This includes seemingly minor purchases such as cough remedies, pain relievers, or vitamin supplements, as some may contain ingredients that affect blood glucose or interact with diabetes medications.

Signs of hypoglycaemia warrant immediate attention and possible medication adjustment. Patients should contact their healthcare provider if they experience frequent episodes of low blood sugar (generally below 4.0 mmol/L), particularly if these occur without obvious cause. Symptoms include trembling, sweating, confusion, rapid heartbeat, and hunger. Severe hypoglycaemia causing unconsciousness or seizures requires emergency medical attention (ring 999).

Allergic reactions require urgent attention. Seek emergency help or ring 999 if you experience swelling of the face, lips, tongue, or throat, difficulty breathing, or severe rash after using Trulicity.

Gastrointestinal symptoms that are severe or persistent beyond the first few weeks of treatment should be discussed with a healthcare professional. Whilst mild nausea is common initially, severe vomiting, persistent diarrhoea, or signs of dehydration may indicate the need for dose adjustment or additional support. Severe abdominal pain, particularly if radiating to the back, could indicate pancreatitis and requires urgent medical assessment.

Changes in other chronic conditions necessitate medication review. For example, if kidney function deteriorates, if cardiovascular medications are adjusted, or if new conditions are diagnosed, the entire medication regimen—including Trulicity—should be reassessed for appropriateness and potential interactions.

Patients should maintain an up-to-date medication list including all prescription drugs, over-the-counter products, and supplements, and bring this to all healthcare appointments. Community pharmacists offer valuable medication review services and can identify potential interactions before they become problematic.

Suspected adverse reactions to Trulicity or any other medicine should be reported via the MHRA Yellow Card Scheme at www.mhra.gov.uk/yellowcard or by searching for MHRA Yellow Card in the Google Play or Apple App Store.

Frequently Asked Questions