Trulicity (dulaglutide) is a once-weekly injectable medication used to improve blood sugar control in adults with type 2 diabetes. As a glucagon-like peptide-1 (GLP-1) receptor agonist, Trulicity mimics a natural hormone that regulates glucose levels through multiple mechanisms. It stimulates insulin release when blood sugar is elevated, reduces glucagon secretion, and slows gastric emptying to prevent post-meal glucose spikes. Approved by the MHRA and available on NHS prescription, Trulicity offers effective glycaemic control alongside potential cardiovascular benefits and modest weight management support when used as part of a comprehensive diabetes treatment plan.

What Is Trulicity and How Does It Work?

Trulicity (dulaglutide) is a prescription medicine used to improve blood sugar control in adults with type 2 diabetes mellitus. It belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists, which work by mimicking the action of a naturally occurring hormone in the body that helps regulate blood glucose levels.

Trulicity is administered as a once-weekly subcutaneous injection using a pre-filled, single-dose pen. The drug is typically prescribed alongside diet and exercise modifications, and may be used alone or in combination with other diabetes medications such as metformin, sulfonylureas, or insulin. Importantly, Trulicity is not indicated for treating type 1 diabetes or diabetic ketoacidosis, and is not a substitute for insulin.

The medication works through multiple complementary mechanisms to lower blood sugar levels. Primarily, it stimulates insulin secretion from the pancreas when blood glucose levels are elevated, whilst simultaneously reducing the release of glucagon, a hormone that raises blood sugar. This glucose-dependent action means that Trulicity carries a lower risk of hypoglycaemia (dangerously low blood sugar) compared to some other diabetes treatments, though this risk increases when used with sulfonylureas or insulin, which may require dose adjustments of these medications.

Beyond glucose control, Trulicity also slows gastric emptying, which means food moves more slowly from the stomach into the small intestine. This helps reduce post-meal blood sugar spikes and can promote a feeling of fullness, potentially supporting weight management. Trulicity is not recommended for patients with severe gastrointestinal disease, including gastroparesis.

The Medicines and Healthcare products Regulatory Agency (MHRA) has approved Trulicity for use in the UK, and it is available on NHS prescription for patients with type 2 diabetes who meet specific clinical criteria outlined in NICE guidance (NG28).

The Mechanism of Action: GLP-1 Receptor Agonists Explained

To understand how Trulicity works, it is essential to appreciate the role of glucagon-like peptide-1 (GLP-1) in normal glucose metabolism. GLP-1 is an incretin hormone naturally produced by cells in the small intestine in response to food intake. It plays a crucial role in maintaining blood sugar balance by enhancing insulin secretion, suppressing glucagon release, and slowing the rate at which the stomach empties.

In people with type 2 diabetes, the incretin effect is often diminished, contributing to poor glycaemic control. Dulaglutide, the active ingredient in Trulicity, is a synthetic analogue of human GLP-1 that has been modified to resist rapid breakdown by the enzyme dipeptidyl peptidase-4 (DPP-4). This modification extends its half-life to approximately five days, making once-weekly dosing feasible.

When Trulicity binds to GLP-1 receptors on pancreatic beta cells, it triggers a cascade of intracellular events that result in increased insulin synthesis and secretion—but only when blood glucose levels are elevated. This glucose-dependent mechanism is a key safety feature, as it significantly reduces the risk of hypoglycaemia. Simultaneously, Trulicity suppresses the release of glucagon from pancreatic alpha cells, further preventing excessive glucose production by the liver.

Additionally, GLP-1 receptor activation in the central nervous system may influence appetite regulation and satiety signals, which can contribute to modest weight loss observed in many patients. The drug also acts on the gastrointestinal tract to delay gastric emptying, smoothing out post-prandial glucose excursions. These multifaceted actions make GLP-1 receptor agonists like Trulicity particularly effective for comprehensive diabetes management, addressing both fasting and post-meal hyperglycaemia.

Cardiovascular benefits have been demonstrated specifically for dulaglutide in the REWIND trial, showing that the medication can reduce major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors.

What to Expect When Starting Trulicity

When initiating Trulicity therapy, patients typically begin with a starting dose of 0.75 mg once weekly, administered subcutaneously in the abdomen, thigh, or upper arm. The injection can be given at any time of day, with or without meals, though maintaining a consistent day each week is recommended. Your healthcare provider may increase the dose to 1.5 mg weekly after at least four weeks if additional glycaemic control is needed, with further stepwise titration possible to 3.0 mg and then to a maximum of 4.5 mg weekly, with at least 4 weeks at each dose level.

Common side effects, particularly during the initial weeks of treatment, include:

• Nausea (reported in up to 20% of patients)

• Diarrhoea or constipation

• Decreased appetite

• Abdominal discomfort or bloating

• Fatigue or mild headache

These gastrointestinal symptoms are usually mild to moderate and tend to diminish as the body adjusts to the medication, typically within 2–4 weeks. Eating smaller, more frequent meals and avoiding high-fat foods may help manage these effects.

If you miss a dose, take it within 3 days of the missed dose. If more than 3 days have passed, skip the missed dose and take your next dose on the regularly scheduled day.

When Trulicity is used with a sulfonylurea or insulin, the risk of hypoglycaemia increases. Your doctor may reduce the dose of these medications to minimise this risk.

Important safety considerations include:

• Pancreatitis: Call 999 or go to A&E if you experience severe, persistent abdominal pain that may radiate to the back, especially if accompanied by vomiting.

• Allergic reactions: Call 999 immediately if you experience severe rash, itching, swelling (especially of the face, lips, tongue), or difficulty breathing. For less severe reactions, contact NHS 111 for advice.

• Gallbladder problems: Contact your GP if you experience upper abdominal pain, fever, or yellowing of skin or eyes.

• Dehydration: Maintain fluid intake, especially if experiencing vomiting or diarrhoea. Seek medical advice if unable to keep fluids down, as this could affect kidney function.

• Diabetic retinopathy: Rapid improvement in blood glucose control may temporarily worsen diabetic eye disease. Attend regular eye screening and report any visual changes promptly.

Trulicity is not recommended during pregnancy or breastfeeding due to limited data. If you are pregnant, planning pregnancy, or breastfeeding, discuss alternative diabetes treatments with your healthcare team.

Report any suspected side effects to the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

Clinical Evidence: How Effective Is Trulicity?

The efficacy of Trulicity has been extensively evaluated through the AWARD (Assessment of Weekly AdministRation of LY2189265 in Diabetes) clinical trial programme, which included multiple phase 3 studies involving thousands of patients with type 2 diabetes. These trials consistently demonstrated significant improvements in glycaemic control across various patient populations.

In the AWARD-2 study, Trulicity 1.5 mg once weekly was compared with once-daily insulin glargine in patients inadequately controlled on metformin and a sulfonylurea. Trulicity achieved non-inferior glycaemic control whilst offering the additional benefit of weight loss compared to weight gain with insulin. This dual benefit of glucose control and weight management is particularly valuable, as obesity is a common comorbidity in type 2 diabetes.

The REWIND trial (Researching Cardiovascular Events with a Weekly Incretin in Diabetes) provided important cardiovascular outcome data. This study of over 9,900 patients followed for a median of 5.4 years demonstrated that Trulicity reduced the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) compared to placebo. Based on these findings, Trulicity is now indicated for reducing cardiovascular risk in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors.

NICE guidance (NG28) recommends GLP-1 receptor agonists like Trulicity as a treatment option for adults with type 2 diabetes when:

• Triple therapy is required (in combination with metformin and another oral drug)

• The patient has a BMI ≥35 kg/m² (or lower thresholds for some ethnic groups) with specific psychological or medical problems associated with obesity

• Insulin therapy would have significant occupational implications or weight loss would benefit other obesity-related comorbidities

Importantly, NICE recommends continuing GLP-1 receptor agonist treatment only if the patient has had a beneficial metabolic response (a reduction of at least 11 mmol/mol [1.0%] in HbA1c and weight loss of at least 3% of initial body weight) after 6 months.

The once-weekly dosing schedule may help some patients maintain their treatment regimen. However, individual responses vary, and ongoing monitoring by your diabetes care team is essential to optimise treatment and adjust therapy as needed.

Frequently Asked Questions