The landscape of metabolic disease management is undergoing a significant transformation, and at the forefront of this evolution is a new class of medications offering profound benefits for individuals with type 2 diabetes and those struggling with weight management. One of the most prominent of these is Mounjaro, the brand name for the drug tirzepatide. Classified as a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, Mounjaro represents a novel approach to glycaemic control and weight loss.

In this review, we will explore its unique mechanism of action, its approved and potential uses, the clinical evidence supporting its efficacy, and its place within the UK healthcare system, including its availability through the NHS and private routes. We will delve into the practical aspects of dosage and administration, the spectrum of potential benefits, and the crucial considerations regarding risks and side effects. 

It is essential to understand that while this article is meticulously researched and detailed, it is for informational purposes only and must not be considered a substitute for professional medical advice. The decision to start, stop, or alter any medical treatment should only be made in consultation with a qualified healthcare provider who can assess your individual health needs and circumstances.

Understanding Tirzepatide: The Dual-Action Mechanism

To truly appreciate the significance of Mounjaro (tirzepatide), one must first understand its sophisticated mechanism of action. Unlike previous generations of incretin-based therapies that targeted a single hormone pathway, tirzepatide is the first-in-class dual GIP and GLP-1 receptor agonist. This means it mimics the effects of two separate, naturally occurring gut hormones that are crucial for metabolic regulation.

The Role of GIP and GLP-1

• Glucagon-Like Peptide-1 (GLP-1): This hormone is released from the intestines after eating. Its functions include stimulating the pancreas to release insulin in response to high blood sugar, suppressing the release of glucagon (a hormone that raises blood sugar), slowing down gastric emptying (making you feel fuller for longer), and acting on the brain to reduce appetite.
• Glucose-Dependent Insulinotropic Polypeptide (GIP): This is another incretin hormone, also released after a meal. It is a potent stimulator of insulin secretion. Interestingly, in individuals with type 2 diabetes, the response to GIP is often impaired. Tirzepatide’s ability to act on GIP receptors may help restore this pathway’s function.

How Tirzepatide Works

By acting as an agonist at both GIP and GLP-1 receptors, tirzepatide orchestrates a multi-pronged attack on the key pathophysiological defects of type 2 diabetes and obesity:

1. Glucose-Dependent Insulin Secretion: A key feature of tirzepatide is that its effect on insulin release is “glucose-dependent.” This means it primarily stimulates the pancreas to release insulin when blood sugar levels are high (e.g., after a meal) and has a minimal effect when blood sugar is normal or low. This intelligent mechanism significantly reduces the risk of hypoglycaemia (low blood sugar) compared to older diabetes medications like sulfonylureas.
2. Glucagon Suppression: Tirzepatide reduces the secretion of glucagon from the pancreas. Glucagon’s primary role is to signal the liver to release stored glucose into the bloodstream. By suppressing glucagon, tirzepatide helps to lower overall blood sugar levels, particularly the fasting blood glucose that is often elevated in type 2 diabetes.
3. Delayed Gastric Emptying and Appetite Regulation: The GLP-1 component of tirzepatide’s action slows the rate at which food leaves the stomach. This contributes to a prolonged feeling of fullness (satiety) after meals. Furthermore, it acts directly on appetite centres in the brain, reducing hunger signals and cravings, which leads to a lower overall calorie intake.

Comparison with GLP-1 Receptor Agonists

The key innovation of tirzepatide is its dual agonism. While single GLP-1 receptor agonists like semaglutide (Ozempic, Wegovy) and liraglutide (Saxenda, Victoza) have been highly effective, the addition of GIP agonism appears to create a synergistic effect. Seminal research, such as the SURPASS-2 clinical trial published in The New England Journal of Medicine, directly compared tirzepatide with semaglutide. The study found that at all tested doses, tirzepatide was superior to semaglutide in both reducing HbA1c levels and promoting weight loss in patients with type 2 diabetes. This suggests that engaging both the GIP and GLP-1 pathways leads to more profound metabolic benefits than targeting the GLP-1 pathway alone.

Pharmacokinetic Profile

Tirzepatide has been engineered for convenience. It has a long half-life of approximately five days, which allows for once-weekly subcutaneous injection. This is achieved by modifications to the molecule that protect it from rapid degradation by the DPP-4 enzyme and allow it to bind to albumin in the blood, creating a circulating reservoir of the drug. This stable, long-acting profile ensures consistent therapeutic levels throughout the week, contributing to its sustained effects on blood sugar and appetite.

Approved and Off-Label Uses of Mounjaro

In the UK and Europe, the regulatory pathway determines how a medication can be prescribed. It’s crucial to distinguish between officially approved (licensed) indications and “off-label” uses, which are common but require careful clinical judgement.

Approved Indication: Type 2 Diabetes Mellitus

The primary licensed indication for Mounjaro in the UK, as approved by the Medicines and Healthcare products Regulatory Agency (MHRA), is for the treatment of adults with insufficiently controlled type 2 diabetes mellitus. It is intended to be used as an adjunct to diet and exercise.

The approval was based on the extensive SURPASS clinical trial programme. These trials consistently demonstrated Mounjaro’s superiority over placebo, other GLP-1 receptor agonists, and various insulin regimens in improving glycaemic control. Key findings across the programme showed:

• Significant HbA1c Reduction: Patients on Mounjaro achieved substantial reductions in their HbA1c levels (a measure of average blood sugar over three months), with many achieving levels below the diabetic threshold.
• High Rates of Glycaemic Control: A significantly higher proportion of patients treated with Mounjaro reached the target HbA1c of less than 7% (53 mmol/mol) compared to those on comparator drugs.

It is vital to remember that Mounjaro is not a replacement for lifestyle changes. Its efficacy is maximised when used in combination with a healthy diet and regular physical activity.

Off-Label Use: Weight Management

While Mounjaro’s effect on weight was a secondary endpoint in the diabetes trials, the results were so striking that they prompted a separate series of trials focused purely on weight loss in individuals with obesity but without diabetes. This was the SURMOUNT trial programme.

The SURMOUNT-1 trial, also published in , was a landmark study. It found that participants taking the highest dose of tirzepatide (15 mg) achieved an average weight loss of 20.9% of their initial body weight over 72 weeks. This level of efficacy approaches that seen with bariatric surgery and was unprecedented for a pharmaceutical intervention at the time.

In the UK, while Mounjaro is licensed for diabetes, another tirzepatide-containing product, Zepbound, has been approved by the MHRA specifically for weight management. However, the practical availability of Zepbound on the NHS is still subject to guidance from the National Institute for Health and Care Excellence (NICE). Consequently, many clinicians in the UK may prescribe Mounjaro “off-label” for weight management, particularly through private clinics.

The Regulatory Framework for Off-Label Prescribing

Prescribing a medication “off-label” is a legal and common practice in the UK. The General Medical Council (GMC) provides guidance stating that doctors may prescribe off-label if they believe it is in the patient’s best interest, there is a sufficient evidence base to support its use, and the patient is fully informed and consents to the treatment. For Mounjaro, the robust data from the SURMOUNT trials provides a strong evidence base for its use in obesity.

Dosage and Administration

Proper dosage, titration, and administration are critical for maximising the benefits of Mounjaro while minimising potential side effects. The treatment follows a structured “start low, go slow” approach.

Available Dosage Strengths

Mounjaro is supplied in a pre-filled, single-use auto-injector pen, known as the KwikPen. The available dosage strengths are:

• 2.5 mg
• 5 mg
• 7.5 mg
• 10 mg
• 12.5 mg
• 15 mg

Each pen is designed to deliver a single dose, making it simple and convenient for patient use.

Recommended Titration Schedule

The goal of titration is to allow the body to gradually adapt to the medication, which primarily helps to mitigate the common gastrointestinal side effects. The standard schedule is as follows:

• Starting Dose: The treatment begins with a 2.5 mg injection once a week for the first four weeks. This dose is not considered therapeutic for glycaemic control but is essential for acclimatisation.
• First Increase: After four weeks, the dose is increased to 5 mg once a week. This is the lowest effective therapeutic dose.
• Further Increases: The dose can be further increased in 2.5 mg increments (to 7.5 mg, 10 mg, 12.5 mg, and finally 15 mg) as needed to achieve individual treatment goals. Each dose level should be maintained for at least four weeks before considering the next increase.

The final maintenance dose will be determined by your healthcare provider based on your individual response, tolerance, and treatment objectives (e.g., HbA1c targets or weight loss goals).

Subcutaneous Injection Technique

Mounjaro is administered as a subcutaneous (under the skin) injection. The process is designed to be straightforward:

• Injection Sites: The recommended injection sites are the abdomen (avoiding the 2-inch area around the navel), the thigh, or the outer surface of the upper arm. It is advisable to rotate injection sites each week to avoid skin irritation.
• Administration: The KwikPen is a simple device. After removing the cap, the pen is pressed firmly against the skin, and a button is pushed to start the injection. The pen will click once to indicate the injection has started and a second time to signal it is complete.
• Timing: The injection can be taken at any time of day, with or without food, on the same day each week.

Handling Missed Doses

If you miss a dose, the guidance is as follows:

• If it has been 4 days (96 hours) or less since the missed dose, take it as soon as you remember. Then, resume your regular weekly schedule.
• If it has been more than 4 days since the missed dose, skip the missed dose entirely and take your next dose on your regularly scheduled day. Do not take two doses at once to make up for a missed one.

Storage

Mounjaro pens must be stored correctly to maintain their efficacy. They should be kept in a refrigerator (between 2°C and 8°C) but should not be frozen. If necessary, individual pens can be kept at room temperature (below 30°C) for up to 21 days.

Potential Benefits of Mounjaro

The clinical trial data for tirzepatide have established it as a highly effective medication with a range of significant metabolic benefits.

Superior Glycaemic Control

For individuals with type 2 diabetes, Mounjaro’s primary benefit is its powerful effect on blood sugar levels.

• HbA1c Reduction: Across the SURPASS trials, Mounjaro demonstrated dose-dependent reductions in HbA1c that were statistically superior to all active comparators, including insulin. At the highest dose, average reductions of up to 2.3 percentage points were observed.
• Diabetes Remission: A remarkable finding from some analyses was the high rate of diabetes remission (defined as achieving a normal HbA1c level without ongoing diabetes medication). A significant portion of participants on Mounjaro were able to achieve this milestone.

Unprecedented Weight Loss

The benefit that has garnered the most public attention is Mounjaro’s profound impact on body weight.

• For Patients with Diabetes: In the SURPASS trials, patients with type 2 diabetes saw average weight loss of up to 15.7% (15.6 kg or 34.4 lbs) from baseline.
• For Patients with Obesity: As noted from the SURMOUNT-1 trial, individuals without diabetes achieved even greater results, with an average weight loss of 20.9% (22.5 kg or 49.6 lbs) at the 15 mg dose. This is a level of efficacy that blurs the line between medical and surgical weight loss interventions.

Cardiometabolic Health Improvements

Beyond glucose and weight, Mounjaro positively impacts a cluster of risk factors associated with cardiovascular disease.

• Blood Pressure: Clinical trials have shown modest but clinically meaningful reductions in both systolic and diastolic blood pressure.
• Lipid Profile: Mounjaro has been shown to improve the lipid profile by lowering triglycerides and LDL (“bad”) cholesterol and, in some cases, increasing HDL (“good”) cholesterol.
• Cardiovascular Outcomes: While the dedicated cardiovascular outcomes trial (SURPASS-CVOT) is still ongoing, preliminary analyses and the known benefits of the GLP-1 class suggest a high likelihood of cardiovascular protection. The results of this trial are eagerly awaited to formally establish Mounjaro’s role in reducing the risk of heart attack, stroke, and cardiovascular death.

Risks, Side Effects, and Contraindications

While Mounjaro offers substantial benefits, it is not without risks and side effects. A thorough understanding of these is essential for any individual considering this treatment.

Common Side Effects

The most frequently reported side effects are gastrointestinal in nature, stemming from the medication’s effect on gastric emptying and the digestive system. These include:

• Nausea
• Diarrhoea
• Vomiting
• Constipation
• Decreased appetite
• Indigestion (dyspepsia)
• Abdominal pain

These side effects are most common when starting the medication or after a dose increase. They are typically mild to moderate in severity and tend to decrease over time as the body adapts. The “start low, go slow” titration schedule is specifically designed to minimise these effects.

Serious Side Effects and Warnings

While less common, there are several serious potential risks that require immediate medical attention.

• Pancreatitis: Inflammation of the pancreas has been reported with incretin mimetics. Patients should be aware of the symptoms, which include severe, persistent abdominal pain that may radiate to the back, with or without vomiting. If pancreatitis is suspected, Mounjaro must be discontinued immediately.
• Gallbladder Problems: There is an increased risk of gallbladder-related issues, including gallstones (cholelithiasis) and gallbladder inflammation (cholecystitis), particularly in the context of rapid weight loss.
• Hypoglycaemia: The risk of low blood sugar is low when Mounjaro is used alone (monotherapy). However, the risk increases significantly when it is used in combination with other medications that can cause hypoglycaemia, such as insulin or sulfonylureas (e.g., gliclazide). Dose adjustments of these concomitant medications are often necessary.
• Thyroid C-Cell Tumours: In rodent studies, tirzepatide caused an increase in thyroid C-cell tumours. While the relevance to humans is unknown, this finding has led to a specific contraindication.

Contraindications

Mounjaro should not be used in individuals with:

• A personal or family history of Medullary Thyroid Carcinoma (MTC).
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• A known serious hypersensitivity to tirzepatide or any of its excipients.

Drug Interactions

Due to its effect on delaying gastric emptying, Mounjaro can potentially affect the absorption of orally administered medications. This is particularly important for drugs with a narrow therapeutic window or those that require rapid absorption, such as oral contraceptives. It is crucial to discuss all medications, including over-the-counter drugs and supplements, with your doctor.

Reporting Side Effects

In the UK, patients and healthcare professionals are encouraged to report any suspected adverse drug reactions through the Yellow Card Scheme. This is a vital system run by the MHRA for monitoring the safety of medicines in real-world use. You can find more information on the Yellow Card Scheme website.

Mounjaro in the UK Healthcare System

Navigating access to new medications in the UK involves understanding the roles of the MHRA, NICE, and the distinction between NHS and private healthcare.

NICE Appraisal and NHS Availability

The National Institute for Health and Care Excellence (NICE) is the body that provides national guidance and advice to improve health and social care. Its technology appraisals determine whether a new medicine is clinically and cost-effective for use within the NHS in England and Wales.

In September 2023, NICE recommended Mounjaro as an option for treating type 2 diabetes in adults, but with specific criteria. It is typically recommended for patients who are also managing their weight and have not achieved adequate control with other oral antidiabetic drugs. The exact criteria can be complex and may involve specific BMI and HbA1c thresholds, as well as failure to respond to other treatments.

For weight management, the situation is different. While the MHRA has licensed Zepbound (tirzepatide) for this use, NICE is still conducting its appraisal to determine if it will be recommended for routine NHS funding. As of mid-2024, access to tirzepatide for weight loss is primarily through the private sector.

The Patient Pathway

• NHS Access (for Type 2 Diabetes): A patient would typically be under the care of a GP or a specialist diabetes team. If they meet the NICE criteria, their doctor can initiate a prescription for Mounjaro. The patient would pay the standard NHS prescription charge per item (in England), unless they are exempt.
• Private Access (for Diabetes or Weight Management): A patient can seek a consultation with a doctor in a private clinic. These are often specialist-led weight management or endocrinology clinics. The doctor will conduct a full assessment to ensure the medication is safe and appropriate. If prescribed, the patient bears the full cost of the medication and the consultation fees. The monthly cost for Mounjaro on a private prescription can be substantial, often running into several hundred pounds.

Cost Considerations

The difference in cost is stark. An NHS prescription is a fixed, subsidised cost. A private prescription reflects the full market price of the drug, which for a new, patented medication like Mounjaro, can be high. At HeMed weight loss programme the pricing starts from £99 and £159 every 4 weeks.  

Patient Considerations and Monitoring

Starting a powerful medication like Mounjaro requires a partnership between the patient and their healthcare provider, involving careful consideration, ongoing monitoring, and a commitment to a holistic treatment plan.

Before Starting Treatment

Before your first injection, it is imperative to have a thorough discussion with a clinician. Be prepared to share:

• A complete medical history, including any past issues with your pancreas, kidneys, or gallbladder.
• Your personal and family history, specifically regarding thyroid cancer.
• A full list of all medications you are taking, including prescription, over-the-counter, and herbal supplements.
• If you are pregnant, planning to become pregnant, or breastfeeding. Mounjaro is generally not recommended in these situations.

Recommended Monitoring

While on Mounjaro, your healthcare team will monitor your progress and safety through regular check-ups. This will likely include:

• Blood Tests: Regular monitoring of your HbA1c to assess glycaemic control, as well as checks on your kidney function (e.g., eGFR) and potentially liver enzymes.
• Weight and BMI: Regular tracking of your weight to assess the efficacy of the treatment for weight management.
• Blood Pressure: Monitoring for changes in blood pressure.
• Side Effect Review: Discussing any side effects you are experiencing to determine if dose adjustments or other management strategies are needed.

The Crucial Role of Lifestyle Modifications

It cannot be overstated: Mounjaro is a tool, not a magic bullet. Its success is profoundly amplified when combined with sustained lifestyle changes. This includes:

• Diet: Adopting a balanced, nutrient-dense diet that is lower in processed foods, sugar, and unhealthy fats. A healthcare provider or registered dietitian can provide personalised advice.
• Exercise: Engaging in regular physical activity, aiming for the NHS-recommended 150 minutes of moderate-intensity activity per week, plus strength exercises.

These lifestyle changes not only enhance the effects of the medication but are also essential for maintaining health benefits in the long term, especially if the medication is ever discontinued.

Future Directions and Research

The story of tirzepatide is still unfolding. Its profound effects on glucose and weight have opened up new avenues of research, and its long-term impact on medicine is likely to be substantial.

Ongoing Clinical Trials

Researchers are actively investigating tirzepatide’s potential in a range of other conditions linked to metabolic dysfunction. Ongoing or planned trials, which can be tracked on registries like ClinicalTrials.gov, are exploring their use in:

• Non-alcoholic steatohepatitis (NASH): A severe form of fatty liver disease.
• Heart Failure with Preserved Ejection Fraction (HFpEF): A type of heart failure strongly associated with obesity.
• Obstructive Sleep Apnoea: A condition often exacerbated by excess weight.
• Kidney Disease: Assessing its potential to protect kidney function in people with type 2 diabetes.

The results of the SURPASS-CVOT trial will be particularly influential, as a positive outcome would firmly establish tirzepatide as a key agent for cardiovascular risk reduction.

Future Formulations

While the once-weekly injection is convenient, research is always underway to develop new delivery methods. The pharmaceutical industry is actively pursuing oral formulations of incretin-based drugs, and it is plausible that an oral version of tirzepatide or a similar dual-agonist could become available in the future, further improving patient accessibility and convenience.

The development of tirzepatide and other next-generation metabolic therapies signals a paradigm shift in how we approach type 2 diabetes and obesity—treating them not just as conditions to be managed, but as diseases with underlying pathophysiologies that can be directly and powerfully targeted.

Conclusion

Mounjaro (tirzepatide) represents a monumental step forward in the management of type 2 diabetes and obesity. Its unique dual-agonist mechanism, targeting both GIP and GLP-1 receptors, delivers unprecedented efficacy in both lowering blood sugar and promoting substantial weight loss. The robust clinical evidence from the SURPASS and SURMOUNT trial programmes has established it as a powerful therapeutic option, offering benefits that extend to blood pressure and lipid profiles, with the potential for significant cardiovascular protection.

However, its power must be respected. The treatment requires a careful, structured approach to dosing to manage the common gastrointestinal side effects. Patients and clinicians must be vigilant for the signs of more serious, albeit rare, adverse events. In the UK, access is currently stratified, with NHS availability governed by strict NICE criteria for type 2 diabetes, while its use for weight management remains largely in the private sector for now.

Ultimately, Mounjaro is a testament to the progress of medical science, offering new hope to millions. Yet, it is crucial to view it within a holistic framework of health. It is a powerful tool that works best when wielded in conjunction with sustained, meaningful lifestyle changes in diet and exercise.

If you believe Mounjaro may be relevant to your health journey, the most important next step is to have an open and detailed conversation with your GP or a specialist healthcare provider like HeMed. They are the only ones who can help you weigh the potential benefits against the risks and decide if this transformative medication is the right choice for you.

References

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