Trulicity and Januvia together is a combination that raises important questions for people managing type 2 diabetes in the UK. Trulicity (dulaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist given as a once-weekly injection, whilst Januvia (sitagliptin) is a dipeptidyl peptidase-4 (DPP-4) inhibitor taken orally once daily. Both medications work through the incretin system to lower blood glucose, but NICE guidance explicitly advises against combining them. If a GLP-1 receptor agonist like Trulicity is started, any existing DPP-4 inhibitor such as Januvia should typically be discontinued. Understanding why this combination is not recommended helps ensure safe, effective diabetes management aligned with UK clinical standards.

Can You Take Trulicity and Januvia Together?

In UK clinical practice, combining Trulicity (dulaglutide) and Januvia (sitagliptin) is generally not recommended according to NICE guidance. These medications belong to different classes of glucose-lowering agents for type 2 diabetes: Trulicity is a glucagon-like peptide-1 (GLP-1) receptor agonist administered as a once-weekly subcutaneous injection, whilst Januvia is a dipeptidyl peptidase-4 (DPP-4) inhibitor taken orally once daily.

Both medications are licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) for use in type 2 diabetes. However, NICE guidance (NG28) advises that if a GLP-1 receptor agonist like Trulicity is initiated, any existing DPP-4 inhibitor such as Januvia should typically be discontinued.

Treatment intensification should follow a stepwise approach, typically starting with metformin and adding further agents based on individual patient factors such as HbA1c levels, cardiovascular risk, renal function, and patient preference. The decision to use diabetes medications in any combination outside standard guidance would usually be made by a diabetes specialist, taking into account your specific clinical circumstances and with a clear rationale and review plan.

It is essential that you never start, stop, or combine diabetes medications without consulting your healthcare team. Your doctor will assess which treatment approach is appropriate for you, monitor your response to treatment, and adjust your medication regimen as needed to optimise glucose control whilst minimising the risk of adverse effects.

How Trulicity and Januvia Work Differently

Understanding how Trulicity and Januvia work helps explain why they are not typically used together in UK practice. Trulicity (dulaglutide) is a GLP-1 receptor agonist that mimics the action of the naturally occurring hormone glucagon-like peptide-1. When administered, it binds to GLP-1 receptors on pancreatic beta cells, stimulating insulin secretion in a glucose-dependent manner—meaning insulin is released only when blood glucose levels are elevated. This reduces the risk of hypoglycaemia compared to some other diabetes medications. Additionally, Trulicity slows gastric emptying, which helps reduce post-meal glucose spikes, and acts on the brain to promote satiety, often leading to weight loss.

Januvia (sitagliptin), on the other hand, is a DPP-4 inhibitor that works by blocking the enzyme dipeptidyl peptidase-4. This enzyme normally breaks down incretin hormones, including the body's own GLP-1. By inhibiting DPP-4, Januvia increases the levels of active incretin hormones in the bloodstream, which in turn enhances insulin secretion and suppresses glucagon release in a glucose-dependent fashion. Unlike Trulicity, Januvia does not significantly slow gastric emptying and is generally weight-neutral.

The key difference lies in their approach: Trulicity provides an external source of GLP-1 receptor stimulation with additional effects on appetite and gastric emptying, whilst Januvia preserves the body's own incretin hormones by preventing their breakdown. Because GLP-1 receptor agonists already provide strong GLP-1 receptor stimulation, adding a DPP-4 inhibitor confers little extra benefit. This is why NICE advises against combining them and recommends discontinuing DPP-4 inhibitors when starting GLP-1 receptor agonists.

Benefits of Combining Trulicity and Januvia

When used together, Trulicity and Januvia may provide only modest additional glycaemic control compared to using Trulicity alone. The complementary mechanisms—external GLP-1 receptor activation from Trulicity and preservation of endogenous incretins by Januvia—have additive effects at best, with the expected incremental HbA1c benefit being small.

It is important to note that NICE guidance (NG28) explicitly advises not to offer a DPP-4 inhibitor in combination with a GLP-1 receptor agonist. If a GLP-1 receptor agonist is started, any existing DPP-4 inhibitor is usually discontinued.

One potential advantage of GLP-1 receptor agonist therapy is the reduced risk of hypoglycaemia. Both medications work in a glucose-dependent manner, meaning they primarily lower blood glucose when levels are elevated, rather than causing excessive insulin release when glucose is already normal or low. This makes them relatively safe from a hypoglycaemia perspective, particularly when compared to sulphonylureas or insulin therapy.

Weight management is another consideration. Trulicity is associated with weight loss in many patients due to its effects on appetite and gastric emptying, whilst Januvia is weight-neutral. Therefore, Trulicity may support modest weight reduction, which is beneficial for many people with type 2 diabetes who are overweight or obese.

Cardiovascular benefits have been demonstrated with Trulicity in clinical trials (REWIND study), showing a reduction in major adverse cardiovascular events in people with established cardiovascular disease or multiple risk factors. Januvia has shown cardiovascular safety but not significant cardiovascular benefit (TECOS study).

For patients with established cardiovascular disease, chronic kidney disease, or high cardiovascular risk, NICE guidance now prioritises SGLT2 inhibitors as the preferred second-line agents after metformin, rather than either GLP-1 receptor agonists or DPP-4 inhibitors.

Side Effects When Taking Both Medications

When taking diabetes medications, you may experience side effects specific to each drug. Understanding these potential adverse effects helps you recognise what is normal and when to seek medical advice.

Gastrointestinal side effects are the most common with Trulicity, particularly when starting treatment or increasing the dose. These include:

• Nausea and vomiting – often mild to moderate and typically improving over several weeks

• Diarrhoea or constipation – affecting bowel habits in some individuals

• Abdominal discomfort or pain – usually transient

• Reduced appetite – which may be beneficial for weight management but can be troublesome for some

These gastrointestinal effects are generally less pronounced with Januvia, though some people may experience mild nausea or abdominal discomfort.

Injection site reactions may occur with Trulicity, including redness, itching, or mild swelling at the injection site. These are usually mild and resolve without intervention.

Pancreatitis is a rare but serious potential side effect associated with both GLP-1 receptor agonists and DPP-4 inhibitors. If pancreatitis is suspected, the medication should be stopped immediately. Seek immediate medical attention if you experience severe, persistent abdominal pain that may radiate to the back, especially if accompanied by vomiting. This requires urgent assessment to rule out pancreatitis. Caution is advised in people with a history of pancreatitis.

GLP-1 receptor agonists have been associated with gallbladder problems. Seek medical advice if you develop right upper abdominal pain, fever, or yellowing of the skin or eyes (jaundice).

DPP-4 inhibitors like Januvia have been associated with bullous pemphigoid, a rare skin condition causing blisters and erosions. If you develop blisters or skin erosions, stop taking Januvia and seek urgent medical advice.

Januvia requires dose adjustment in moderate to severe renal impairment. Your doctor should check your kidney function before and during treatment.

Hypoglycaemia risk is generally low with these medications when used without other glucose-lowering medications such as sulphonylureas or insulin. However, if you are taking additional diabetes medications, your risk of low blood glucose may increase, and dose adjustments may be necessary.

For signs of severe allergic reaction (swelling of face/lips/tongue, breathing difficulty, collapse), call 999 immediately.

Report any suspected side effects to the MHRA Yellow Card Scheme at yellowcard.mhra.gov.uk or via the Yellow Card app.

NHS Guidance on Using Trulicity with Januvia

NICE guidance (NG28) on type 2 diabetes management provides a structured approach to treatment intensification and explicitly states: do not offer a DPP-4 inhibitor in combination with a GLP-1 receptor agonist. If a GLP-1 receptor agonist like Trulicity is initiated, any existing DPP-4 inhibitor such as Januvia should typically be discontinued.

The NICE-recommended approach involves starting with metformin as first-line therapy, then adding a second agent if HbA1c remains above target. Options for second-line therapy include DPP-4 inhibitors, SGLT2 inhibitors, sulphonylureas, or GLP-1 receptor agonists, depending on individual circumstances. For people with established cardiovascular disease, chronic kidney disease, or high cardiovascular risk, SGLT2 inhibitors are now the preferred second-line agents.

GLP-1 receptor agonists like Trulicity are particularly recommended for people with a BMI of 35 kg/m² or higher (or lower thresholds for certain ethnic groups) or when weight loss would benefit other obesity-related comorbidities. NICE recommends that GLP-1 receptor agonists should be reviewed after 6 months and only continued if the person 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).

Combining a GLP-1 receptor agonist with a DPP-4 inhibitor is not recommended because both work through the incretin system, and the additional glucose-lowering benefit of using both together is modest. The cost-effectiveness of such a combination is also questionable.

However, clinical practice may vary, and there may be specific circumstances where a diabetes specialist considers an alternative treatment approach appropriate for an individual patient. This might occur in complex cases where other treatment options are limited due to contraindications, intolerances, or patient-specific factors.

If you are prescribed diabetes medications, your healthcare team should:

• Clearly explain the rationale for your treatment plan

• Monitor your HbA1c regularly (typically every 3–6 months)

• Review the continued need for your medications

• Assess for side effects and treatment response

• Consider alternative treatment strategies if glucose control remains inadequate

Regular medication reviews are essential to ensure your diabetes treatment remains optimal, cost-effective, and aligned with current best practice. If you have questions about your medications, discuss this with your GP or diabetes specialist nurse, who can explain the specific reasons for your treatment plan.

Frequently Asked Questions