Different strengths of Trulicity (dulaglutide) allow healthcare professionals to tailor type 2 diabetes treatment to individual patient needs. Available in four doses—0.75 mg, 1.5 mg, 3 mg, and 4.5 mg—this once-weekly GLP-1 receptor agonist offers flexible dose escalation based on glycaemic response and tolerability. Understanding the distinctions between these strengths helps patients and clinicians optimise blood sugar control whilst managing potential side effects. This article explores how each Trulicity strength works, when dose adjustments may be appropriate, and what factors influence prescribing decisions in UK clinical practice, aligned with NICE and MHRA guidance.

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 in the body that helps regulate blood sugar levels.

The mechanism of action of Trulicity involves several complementary pathways. Firstly, it stimulates insulin secretion from the pancreas in a glucose-dependent manner—meaning it only triggers insulin release when blood sugar levels are elevated, thereby reducing the risk of hypoglycaemia. Secondly, dulaglutide suppresses glucagon secretion, a hormone that raises blood glucose, particularly after meals. Thirdly, it slows gastric emptying, which helps moderate the rate at which glucose enters the bloodstream following food intake. Additionally, many patients experience modest weight loss, which can further improve glycaemic control and cardiovascular risk factors.

Trulicity is administered via a pre-filled, single-use pen that delivers the medication subcutaneously (under the skin), typically into the abdomen, thigh, or upper arm. The once-weekly dosing schedule offers convenience compared to daily injectable therapies, potentially improving adherence. In the UK, Trulicity is licensed for use either as monotherapy (when metformin is inappropriate) or in combination with other glucose-lowering medications, including metformin, sulfonylureas, sodium-glucose co-transporter-2 (SGLT2) inhibitors, or insulin.

Importantly, Trulicity is not indicated for type 1 diabetes or diabetic ketoacidosis, and caution is advised in patients with severe gastrointestinal disease. If you experience severe, persistent abdominal pain, you should stop taking Trulicity and seek urgent medical advice, as this could indicate pancreatitis. NICE guidance (NG28) supports the use of GLP-1 receptor agonists like Trulicity in specific clinical scenarios where glycaemic targets are not achieved with existing therapy.

Available Strengths of Trulicity in the UK

Trulicity is available in the UK in four different strengths, each delivered in a pre-filled, single-dose pen. These strengths are:

• 0.75 mg – the recommended starting dose

• 1.5 mg – the first step-up dose

• 3 mg – an intermediate higher dose

• 4.5 mg – the maximum licensed dose

Each pen contains a fixed dose of dulaglutide in a 0.5 mL solution, designed for subcutaneous injection once weekly. According to the UK product licence, treatment should be initiated with the 0.75 mg strength once weekly. After at least 4 weeks, if additional glycaemic control is needed, the dose can be increased to 1.5 mg once weekly.

The higher strengths—3 mg and 4.5 mg—were introduced more recently to provide additional glycaemic control for patients who require intensification beyond the 1.5 mg dose. These higher doses have demonstrated superior HbA1c reductions in clinical trials compared to lower strengths, whilst maintaining an acceptable safety profile. The availability of multiple strengths allows for individualised dose titration, enabling healthcare professionals to tailor treatment according to each patient's glycaemic response, tolerability, and therapeutic goals.

All strengths are administered using the same user-friendly pen device, which requires no dose adjustment or preparation by the patient, thereby minimising the risk of dosing errors. Trulicity should be administered on the same day each week. If a dose is missed, it should be administered within 3 days of the missed dose. If more than 3 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.

How Your Doctor Chooses the Right Trulicity Strength

The selection of an appropriate Trulicity strength is a personalised clinical decision based on multiple factors. Your doctor will consider your current glycaemic control (typically measured by HbA1c levels), existing diabetes medications, kidney function, body weight, history of gastrointestinal problems, and your individual treatment goals.

For most patients initiating Trulicity, the 0.75 mg once-weekly dose serves as the recommended starting point, as specified in the UK product licence. This dose provides meaningful HbA1c reductions (typically 0.8–1.5% or approximately 9–16 mmol/mol from baseline) whilst allowing the body to adjust to the medication. If you have a history of significant gastrointestinal sensitivity, your doctor may maintain this dose for a longer period before considering any increase.

Whilst no dose adjustment is required for patients with renal impairment (including those with end-stage renal disease), your doctor will monitor your hydration status and kidney function if you experience significant gastrointestinal side effects. Additionally, if you are taking medications that increase hypoglycaemia risk—particularly sulfonylureas or insulin—your doctor may need to reduce the doses of these agents when starting Trulicity to prevent low blood sugar episodes.

NICE guidance (NG28) recommends considering GLP-1 receptor agonists like Trulicity when patients have inadequate glycaemic control despite optimal doses of other therapies, particularly if weight loss would be beneficial. According to current NICE recommendations, treatment should only be continued if there is a beneficial metabolic response (a reduction of at least 11 mmol/mol [1%] in HbA1c and weight loss of at least 3% of initial body weight in 6 months). It's also worth noting that GLP-1 receptor agonists should not be combined with DPP-4 inhibitors in UK practice.

Adjusting Your Trulicity Dose Over Time

Dose adjustment of Trulicity follows a stepwise titration approach based on your glycaemic response and tolerability. After initiating treatment with the 0.75 mg dose, your doctor will typically monitor your response for at least 4 weeks before considering any dose increase. If additional glycaemic control is needed, the dose may be increased to 1.5 mg once weekly.

The complete titration pathway involves increasing from 0.75 mg to 1.5 mg, then to 3 mg, and subsequently to 4.5 mg if further glycaemic improvement is needed. These increases are made at intervals of at least 4 weeks, allowing sufficient time for the medication to reach steady-state levels and for your body to adapt. The gradual escalation approach helps minimise gastrointestinal side effects, which tend to be more pronounced with abrupt dose increases.

Clinical trial data demonstrate that higher doses provide incremental HbA1c reductions. For instance, the 3 mg dose typically achieves approximately 0.2–0.4% greater HbA1c reduction compared to 1.5 mg, whilst the 4.5 mg dose offers further modest improvements. However, the decision to escalate is not based solely on glycaemic metrics—your doctor will also consider factors such as weight loss achieved, cardiovascular risk profile, and any side effects experienced.

It is important to note that dose reduction may occasionally be necessary if you experience persistent gastrointestinal symptoms or other tolerability issues. If you experience significant vomiting or diarrhoea, it's important to maintain adequate hydration and seek medical advice, as your doctor may need to review your treatment. If you miss a dose, you should administer it within 3 days of the scheduled time. If more than 3 days have passed, skip the missed dose and take the next one on your regular day. Always consult your healthcare team before making any changes to your prescribed dose.

Comparing Trulicity Strengths: Efficacy and Side Effects

Understanding the efficacy and safety profile across different Trulicity strengths helps contextualise treatment decisions. Clinical trials, including the AWARD programme (particularly AWARD-11), have systematically evaluated the various doses, providing robust evidence for their comparative benefits and risks.

Efficacy differences between strengths are dose-dependent but show diminishing returns at higher doses. The 0.75 mg dose typically reduces HbA1c by 0.7–1.3% (8–14 mmol/mol) from baseline, the 1.5 mg dose by 0.8–1.5% (9–16 mmol/mol), whilst the 3 mg dose achieves reductions of approximately 1.1–1.6% (12–17 mmol/mol), and the 4.5 mg dose produces reductions of 1.2–1.8% (13–20 mmol/mol). These higher doses also tend to produce greater weight loss, with patients on 4.5 mg losing an average of 3–4 kg compared to 2–3 kg with 1.5 mg over 6 months. However, individual responses vary considerably, and some patients achieve excellent control on lower doses.

Regarding side effects, gastrointestinal symptoms—particularly nausea, diarrhoea, vomiting, and abdominal discomfort—are the most commonly reported adverse effects across all strengths. These symptoms are typically mild to moderate and tend to diminish over time as the body adapts. However, higher doses (3 mg and 4.5 mg) are associated with a slightly increased incidence of gastrointestinal side effects compared to 1.5 mg, though most patients still tolerate them well.

Other considerations include the risk of hypoglycaemia, which remains low with Trulicity monotherapy but increases when combined with sulfonylureas or insulin. If you experience severe, persistent abdominal pain, you should discontinue Trulicity immediately and seek urgent medical advice, as this could indicate pancreatitis. If pancreatitis is confirmed, treatment should not be restarted. Thyroid C-cell tumours have been observed in rodent studies with GLP-1 receptor agonists, though the relevance to humans is unknown and there is no established causal risk in humans.

If you experience any suspected side effects, you can report them via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk). Overall, the choice of strength represents a balance between maximising glycaemic benefit and minimising side effects, tailored to individual patient circumstances.

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