Mounjaro (tirzepatide) is a once-weekly injectable medication licensed in the UK for type 2 diabetes and chronic weight management. Whilst often discussed alongside GLP-1 receptor agonists such as semaglutide and liraglutide, Mounjaro is technically a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. This dual mechanism distinguishes it from traditional GLP-1 therapies, which target only the GLP-1 pathway. Understanding how Mounjaro works, its approved uses, and how it compares to other treatments is essential for patients and healthcare professionals considering this therapy.

What Is Mounjaro and How Does It Work?

Mounjaro (tirzepatide) is an injectable medication licensed for the treatment of type 2 diabetes mellitus and chronic weight management. Manufactured by Eli Lilly, it represents a novel class of therapy known as a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. This dual mechanism distinguishes Mounjaro from traditional GLP-1 receptor agonists, which target only the GLP-1 pathway.

The medication works by mimicking the action of two naturally occurring incretin hormones: GIP and GLP-1. These hormones are released by the gut in response to food intake and play crucial roles in glucose regulation. By activating both GIP and GLP-1 receptors, tirzepatide enhances insulin secretion in a glucose-dependent manner, meaning insulin is released primarily when blood glucose levels are elevated. This reduces the risk of hypoglycaemia compared to some other diabetes treatments, although the risk increases when used with insulin or sulfonylureas.

Additionally, Mounjaro slows gastric emptying, which prolongs the feeling of fullness after meals, and suppresses glucagon secretion, a hormone that raises blood glucose. The combined effect leads to improved glycaemic control and significant weight loss. In clinical trials, tirzepatide has shown substantial reductions in HbA1c and body weight, with effects varying by dose and patient population.

Mounjaro is administered once weekly via subcutaneous injection, typically in the abdomen, thigh, or upper arm. According to the UK SmPC, dosing starts at 2.5 mg once weekly for 4 weeks, then increases in 2.5 mg increments every 4 weeks until the target dose (5 mg, 7.5 mg, 10 mg, 12.5 mg or 15 mg) is reached, based on individual response and tolerability.

Important safety considerations include risks of acute pancreatitis (seek medical attention for severe abdominal pain with or without vomiting), gallbladder disease, dehydration, and potential worsening of diabetic retinopathy with rapid improvement in glucose control. Mounjaro may reduce the effectiveness of oral contraceptives; additional or non-oral contraception is recommended for 4 weeks after starting treatment and after each dose increase. The medication is not recommended during pregnancy, breastfeeding, or for people under 18 years of age.

Mounjaro's Approved Uses in the UK

In the United Kingdom, Mounjaro has received marketing authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) for two primary indications. The first is as an adjunct to diet and exercise for the treatment of adults with type 2 diabetes mellitus. It is typically prescribed when other glucose-lowering therapies, such as metformin, have not achieved adequate glycaemic control.

The second approved indication is for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or those who are overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity, such as hypertension, dyslipidaemia, or obstructive sleep apnoea. In the SURMOUNT-1 trial, participants without diabetes lost an average of 15-20% of their body weight over 72 weeks at the 10 mg and 15 mg doses, though results may vary in different populations.

While Mounjaro has marketing authorisation for these indications, NHS availability is determined by NICE guidance. For type 2 diabetes, NICE has established specific criteria for NHS-funded use, including previous treatment history and glycaemic targets. For weight management, NHS treatment is typically initiated within specialist weight management services, with specific BMI thresholds, comorbidity requirements, and continuation criteria that must be met.

It is important to note that Mounjaro is not licensed for type 1 diabetes or diabetic ketoacidosis. It should not be used concurrently with other GLP-1 receptor agonists. Patients should be counselled that the medication is part of a comprehensive treatment plan that includes lifestyle modification, dietary changes, and regular physical activity.

Regular monitoring is essential to assess treatment efficacy and adjust therapy as needed. This includes blood glucose, HbA1c, body weight, and assessment for potential side effects. Patients with risk factors for pancreatitis, gallbladder disease, or significant diabetic retinopathy require particular attention during treatment.

Comparing Mounjaro to Other GLP-1 Treatments

When comparing Mounjaro to established GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy), dulaglutide (Trulicity), and liraglutide (Victoza, Saxenda), several key differences emerge. The most significant distinction is Mounjaro's dual agonist mechanism. While traditional GLP-1 agonists activate only GLP-1 receptors, tirzepatide also stimulates GIP receptors.

In the SURPASS-2 clinical trial, Mounjaro demonstrated greater HbA1c reductions compared to semaglutide 1 mg, with mean reductions of up to 2.3% (25 mmol/mol) from baseline at the 15 mg dose. Weight loss outcomes were also more pronounced in this trial. For weight management specifically, comparisons should reference the higher 2.4 mg dose of semaglutide (Wegovy) rather than the 1 mg dose used for diabetes.

In terms of administration, Mounjaro is given once weekly, similar to semaglutide and dulaglutide, which offers convenience compared to daily injections like liraglutide. The side effect profile is broadly comparable across these therapies, with gastrointestinal symptoms—nausea, vomiting, diarrhoea, and constipation—being the most common. These are typically mild to moderate and diminish over time with dose titration.

All these medications carry risks of uncommon but serious adverse effects, including pancreatitis and gallbladder disease. When used with insulin or sulfonylureas, dose adjustments of these medications may be needed to reduce hypoglycaemia risk. Tirzepatide, like other agents in this class, requires monitoring for dehydration and potential effects on diabetic retinopathy, particularly during rapid improvement in glucose control.

Prescribing decisions should be individualised, considering the patient's specific needs, comorbidities, and treatment goals. Local NHS formularies and NICE guidance will influence which treatments are available through the NHS. Shared decision-making between clinician and patient is essential when choosing between these agents.

Is Mounjaro a GLP-1 Receptor Agonist?

The question of whether Mounjaro is a GLP-1 receptor agonist is nuanced. Technically, Mounjaro is not a pure GLP-1 receptor agonist; rather, it is a dual GIP/GLP-1 receptor agonist. This means it activates both the GIP receptor and the GLP-1 receptor simultaneously, making it pharmacologically distinct from traditional GLP-1 agonists.

However, because Mounjaro does activate GLP-1 receptors as part of its mechanism of action, it is often grouped with GLP-1-based therapies in clinical discussions and treatment algorithms. The GLP-1 component is responsible for many of the medication's beneficial effects, including enhanced insulin secretion, reduced glucagon release, delayed gastric emptying, and appetite suppression. The additional GIP receptor activation contributes to its overall efficacy profile.

From a regulatory and classification perspective, tirzepatide represents a distinct therapeutic class. The MHRA and European Medicines Agency (EMA) describe it in the Summary of Product Characteristics as a dual GIP/GLP-1 receptor agonist, acknowledging its dual mechanism. This classification helps healthcare professionals understand its pharmacological profile and clinical effects.

For patients and healthcare professionals, the key takeaway is that while Mounjaro shares many characteristics with GLP-1 receptor agonists—including similar side effects, administration route, and clinical indications—it has a dual mechanism that targets both GIP and GLP-1 receptors. Patients considering Mounjaro should discuss with their GP or diabetes specialist whether this therapy is appropriate for their individual circumstances, taking into account their treatment history, comorbidities, and personal preferences.

As with all medications, patients should report any suspected side effects to their healthcare provider or directly to the MHRA through the Yellow Card scheme (yellowcard.mhra.gov.uk or the Yellow Card app).

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