Trulicity (dulaglutide) is a once-weekly injectable medication used to manage type 2 diabetes mellitus in adults. As a glucagon-like peptide-1 (GLP-1) receptor agonist, it helps regulate blood glucose by stimulating insulin secretion, suppressing glucagon release, and slowing gastric emptying. The highest dose of Trulicity licensed in the UK is 4.5 mg once weekly, reserved for patients requiring maximum glycaemic control after trialling lower doses. Understanding the available dose strengths, appropriate escalation, and safety considerations is essential for optimising treatment outcomes whilst minimising side effects. This article explores Trulicity dosing, including when the maximum dose may be appropriate and important monitoring requirements.

What Is Trulicity and How Does It Work?

Trulicity (dulaglutide) is a once-weekly injectable medication used primarily for the management of type 2 diabetes mellitus in adults. It belongs to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists, which work by mimicking the action of naturally occurring incretin hormones in the body.

The mechanism of action of Trulicity involves several complementary pathways that help regulate blood glucose levels. When administered, dulaglutide binds to GLP-1 receptors on pancreatic beta cells, stimulating glucose-dependent insulin secretion. This means insulin is released only when blood glucose levels are elevated, reducing the risk of hypoglycaemia compared to some other diabetes medications. Additionally, Trulicity suppresses the inappropriate secretion of glucagon—a hormone that raises blood glucose—particularly after meals when glucagon levels should naturally decrease.

Beyond its effects on insulin and glucagon, Trulicity also slows gastric emptying, which helps moderate the rate at which glucose enters the bloodstream following food intake. Many patients also experience a reduction in appetite and subsequent weight loss, which can be beneficial given the strong association between obesity and type 2 diabetes. Clinical trials have demonstrated that Trulicity not only improves glycaemic control (as measured by HbA1c reduction) but may also offer cardiovascular benefits in patients with established cardiovascular disease or multiple risk factors. These cardiovascular outcome benefits were demonstrated in the REWIND trial using the 1.5 mg dose.

Trulicity is licensed in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) and is recommended by NICE (NG28) as a treatment option for type 2 diabetes when certain criteria are met, typically when metformin alone or in combination with other agents has not achieved adequate glycaemic control.

Importantly, Trulicity is not indicated for the treatment of type 1 diabetes or diabetic ketoacidosis.

Available Trulicity Doses in the UK

Trulicity is available in the UK in four different dose strengths, each supplied as a pre-filled, single-use pen injector for subcutaneous administration. The available doses are:

• 0.75 mg once weekly

• 1.5 mg once weekly

• 3 mg once weekly

• 4.5 mg once weekly

According to the UK Summary of Product Characteristics (SmPC), the 0.75 mg dose is the recommended starting dose for most patients beginning Trulicity therapy. This initial dose allows patients to adjust to the medication while minimising the risk of gastrointestinal adverse effects such as nausea, vomiting, and diarrhoea, which are common when initiating GLP-1 receptor agonists.

After at least four weeks on the 0.75 mg dose, patients who require additional glycaemic control can have their dose increased to 1.5 mg once weekly. This dose provides effective glycaemic control for many patients with type 2 diabetes.

For patients who still require additional glycaemic control after at least four weeks on the 1.5 mg dose, the dose can be further increased to 3 mg once weekly. This intermediate dose offers enhanced HbA1c reduction whilst maintaining a manageable side effect profile.

The 4.5 mg dose represents the highest available strength and is reserved for patients who need maximum glycaemic benefit. Dose escalation should always be gradual, with at least four weeks between increases, to allow assessment of therapeutic response and tolerability.

Each pen is colour-coded and clearly labelled to prevent dosing errors, and patients should be counselled on the importance of using the correct strength as prescribed by their healthcare professional. Patients should also be advised on proper injection technique, rotating injection sites, and what to do if a dose is missed (if there are at least 3 days until the next scheduled dose, take it as soon as possible; otherwise, skip the missed dose and take the next dose on the scheduled day).

What Is the Highest Dose of Trulicity?

The highest licensed dose of Trulicity available in the UK is 4.5 mg administered once weekly via subcutaneous injection. This maximum dose was approved following clinical trials, particularly the AWARD-11 study, that demonstrated superior glycaemic efficacy compared to lower doses, with significant reductions in HbA1c levels and body weight in patients with type 2 diabetes.

The 4.5 mg dose is intended for patients who have not achieved adequate blood glucose control on lower doses of Trulicity (0.75 mg, 1.5 mg or 3 mg) after an appropriate trial period, typically at least four weeks at each dose level. NICE guidance supports the use of GLP-1 receptor agonists like Trulicity when treatment intensification is needed, and the 4.5 mg dose provides the maximum therapeutic effect available from this medication.

Clinical trial data from the AWARD programme demonstrated that the 4.5 mg dose produced clinically meaningful HbA1c reductions and weight loss compared to lower doses. The AWARD-11 trial specifically compared the 3 mg and 4.5 mg doses with the 1.5 mg dose over 52 weeks, showing greater efficacy with the higher doses. While cardiovascular safety was maintained at higher doses in clinical trials, it's important to note that the established cardiovascular outcome benefits of dulaglutide (from the REWIND trial) were demonstrated specifically with the 1.5 mg dose.

It is essential to understand that not all patients will require or be suitable for the maximum 4.5 mg dose. Dose selection should be individualised based on glycaemic response, tolerability, patient preferences, and clinical circumstances. Some patients achieve their target HbA1c levels on 0.75 mg, 1.5 mg or 3 mg and do not need further escalation. The principle of using the lowest effective dose to achieve treatment goals whilst minimising side effects remains a cornerstone of good prescribing practice. Patients should never adjust their Trulicity dose without consulting their diabetes healthcare team.

Safety Considerations for Higher Trulicity Doses

Whilst the 4.5 mg dose of Trulicity offers enhanced glycaemic control, it is associated with a higher incidence of gastrointestinal side effects compared to lower doses. The most commonly reported adverse effects include:

• Nausea (affecting up to 20–30% of patients at higher doses)

• Diarrhoea

• Vomiting

• Abdominal pain or discomfort

• Decreased appetite

These side effects are typically most pronounced during the first few weeks after starting treatment or increasing the dose, and often diminish over time as the body adjusts. Consuming smaller, more frequent meals that are low in fat, and staying well hydrated can help manage these symptoms. However, if gastrointestinal side effects are severe or persistent, patients should contact their GP or diabetes nurse for advice, as dose reduction may be necessary.

Pancreatitis is a rare but serious potential adverse effect associated with GLP-1 receptor agonists. Patients should be counselled to seek immediate medical attention if they experience severe, persistent abdominal pain that may radiate to the back, particularly if accompanied by vomiting. If pancreatitis is suspected, Trulicity should be discontinued immediately. There is no definitive evidence that higher doses increase pancreatitis risk, but vigilance remains important.

Other safety considerations include the potential for hypoglycaemia, particularly when Trulicity is used in combination with insulin or sulphonylureas. Whilst Trulicity alone rarely causes hypoglycaemia due to its glucose-dependent mechanism, dose adjustments of concomitant medications may be required when escalating to higher Trulicity doses.

Renal function should be monitored, especially in patients experiencing significant gastrointestinal side effects leading to dehydration, as acute kidney injury has been reported in such cases. While no dose adjustment is required for renal impairment, caution should be exercised in patients with end-stage renal disease due to limited clinical experience.

Trulicity is not recommended in patients with severe gastrointestinal disease, including severe gastroparesis. Patients with diabetic retinopathy should be monitored for progression of retinopathy, particularly during rapid improvement in glycaemic control. Small increases in heart rate and PR interval have also been observed with Trulicity treatment.

Animal studies have shown an increased incidence of thyroid C-cell tumours at clinically relevant exposures, though the relevance to humans is unknown. Routine monitoring of calcitonin is not recommended unless clinically indicated.

Monitoring and Adjusting Your Trulicity Treatment

Effective management of type 2 diabetes with Trulicity requires regular monitoring and ongoing assessment by your healthcare team. When initiating or escalating Trulicity doses, several parameters should be tracked to ensure both efficacy and safety.

HbA1c monitoring is the primary measure of glycaemic control and should typically be checked every 3–6 months once treatment is stable, or more frequently when doses are being adjusted. Your diabetes team will work with you to establish individualised HbA1c targets, commonly around 48–53 mmol/mol (6.5–7.0%) for most adults with type 2 diabetes, though targets may be relaxed in older patients or those with significant comorbidities.

Self-monitoring of blood glucose may be recommended, particularly if you are taking Trulicity alongside medications that can cause hypoglycaemia, such as insulin or sulphonylureas. Your healthcare professional will advise on appropriate testing frequency and target ranges. Report any episodes of hypoglycaemia (blood glucose <4 mmol/L) or symptoms such as tremor, sweating, confusion, or palpitations to your diabetes team, as medication adjustments may be needed.

Body weight and BMI should be tracked regularly, as weight loss is a common beneficial effect of Trulicity. Significant unintended weight loss, however, should be investigated. Renal function (serum creatinine and eGFR) should be monitored at least annually, or more frequently in patients with existing kidney disease or those experiencing gastrointestinal side effects.

If you miss a dose of Trulicity, administer it as soon as possible if there are at least 3 days until your next scheduled dose. If less than 3 days remain, skip the missed dose and take your next dose on the regularly scheduled day.

Ensure you rotate injection sites with each dose to prevent lipodystrophy and maintain consistent absorption. Suitable injection sites include the abdomen, thigh, or upper arm.

Patients should be encouraged to report any adverse effects, particularly persistent nausea, vomiting, diarrhoea, or abdominal pain. If side effects are intolerable despite supportive measures, dose reduction or switching to an alternative medication may be considered. Regular diabetes reviews provide an opportunity to assess injection technique, discuss any concerns, and reinforce the importance of lifestyle measures including diet, physical activity, and smoking cessation.

When to contact your GP or diabetes team:

• Severe or persistent abdominal pain

• Repeated episodes of hypoglycaemia

• Signs of dehydration (reduced urine output, dizziness, dry mouth)

• Unexplained weight loss or gain

• Any new or concerning symptoms

• If planning pregnancy or if you become pregnant (Trulicity is not recommended during pregnancy or breastfeeding)

Remember that Trulicity is not indicated for type 1 diabetes or diabetic ketoacidosis.

Your healthcare team will work collaboratively with you to optimise your Trulicity dose and overall diabetes management plan, ensuring the best possible outcomes whilst maintaining your safety and quality of life.

If you experience any suspected side effects, report them to the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk or via the Yellow Card app).

Frequently Asked Questions