Mounjaro (tirzepatide) is a relatively new diabetes medication that has generated considerable clinical interest since its approval. First authorised by the US Food and Drug Administration in May 2022, Mounjaro became available in the UK following MHRA approval in October 2022. As of early 2025, this medication has been on the market for approximately two and a half years. Mounjaro represents the first dual GIP and GLP-1 receptor agonist approved for type 2 diabetes, offering a novel mechanism of action that distinguishes it from established incretin-based therapies. Understanding its timeline helps patients and clinicians contextualise its evidence base and real-world experience.

When Was Mounjaro First Approved?

Mounjaro (tirzepatide) is a relatively new medication in the landscape of diabetes treatment, having received its first regulatory approval in May 2022. The United States Food and Drug Administration (FDA) granted approval for tirzepatide as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus. This marked a significant milestone as Mounjaro became the first dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist to reach the market.

In the United Kingdom, the Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorisation for Mounjaro in October 2022, approximately five months after the US approval. The European Medicines Agency (EMA) similarly granted marketing authorisation for tirzepatide across the European Union in September 2022. These approvals were based on the comprehensive SURPASS clinical trial programme, which demonstrated effective glycaemic control and weight reduction compared to existing diabetes treatments.

Key approval milestones include:

• May 2022 – FDA approval in the United States

• October 2022 – MHRA approval in the United Kingdom

• September 2022 – EMA approval for the European Union

As of early 2025, Mounjaro has therefore been available for approximately two and a half years, making it one of the newest options in the diabetes medication arsenal. Whilst this represents a relatively short time in pharmaceutical terms, the medication has generated substantial clinical interest due to its novel dual-action mechanism and efficacy data from pre-approval studies.

Mounjaro's Development Timeline and Clinical Trials

The development of tirzepatide began well before its 2022 approval, with Eli Lilly and Company initiating research into dual GIP/GLP-1 receptor agonists in the early 2010s. The first human trials commenced around 2014, with phase 1 studies evaluating safety, tolerability, and pharmacokinetics in healthy volunteers and patients with type 2 diabetes. These early studies established the foundation for understanding tirzepatide's unique mechanism of action and optimal dosing strategies.

The pivotal SURPASS clinical trial programme represented the cornerstone of Mounjaro's development, encompassing multiple phase 3 studies that enrolled over 10,000 participants globally. SURPASS-1 through SURPASS-5 evaluated tirzepatide across diverse patient populations, including treatment-naïve patients and those inadequately controlled on existing therapies such as metformin, insulin, or SGLT2 inhibitors. These trials, conducted between 2018 and 2021, demonstrated HbA1c reductions of 1.8% to 2.4% and weight loss averaging 7 to 12 kg, depending on the dose.

Notably, the SURPASS-2 trial directly compared tirzepatide to semaglutide 1 mg (Ozempic), showing greater glycaemic control and weight reduction with tirzepatide at 40 weeks. The SURPASS-4 trial, which studied tirzepatide in patients with type 2 diabetes at high cardiovascular risk, included exploratory cardiovascular endpoints but was not designed as a definitive cardiovascular outcomes trial. The ongoing SURPASS-CVOT trial, expected to conclude in 2025, is specifically designed to evaluate cardiovascular outcomes with tirzepatide.

The development timeline also included extensive safety monitoring, with particular attention to gastrointestinal tolerability, pancreatitis risk, and thyroid safety—concerns relevant to the incretin-based drug class. This rigorous evaluation process, spanning nearly a decade from initial concept to regulatory approval, reflects the comprehensive approach required for novel diabetes therapeutics.

UK Availability and NHS Access to Mounjaro

Following MHRA approval in October 2022, Mounjaro became available through private prescription in the UK relatively quickly. However, NHS access has followed a more measured pathway, as is typical for new medications requiring health technology assessment. The National Institute for Health and Care Excellence (NICE) published its technology appraisal guidance (TA924) in September 2023, recommending tirzepatide as an option for treating type 2 diabetes in specific circumstances.

NICE recommends Mounjaro for adults with type 2 diabetes when:

• It is used according to the recommendations for GLP-1 receptor agonists in NICE guideline NG28 on type 2 diabetes in adults

• The person has a BMI of at least 35 kg/m² (adjusted to 32.5 kg/m² for people from South Asian, Chinese, other Asian, Middle Eastern, Black African, or African-Caribbean family backgrounds) and specific psychological or medical problems associated with obesity, or

• The person has a BMI lower than 35 kg/m² (adjusted as above), and insulin treatment would have significant occupational implications, or weight loss would benefit other significant obesity-related comorbidities

In line with NG28, treatment should only be continued if there is 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).

NHS availability has been implemented gradually across different integrated care boards (ICBs), with some areas experiencing supply constraints during 2023 and early 2024, as noted in NHS England supply disruption alerts. Eli Lilly has worked to scale up manufacturing capacity to meet global demand, which has affected availability in the UK market. Patients seeking Mounjaro through the NHS should discuss eligibility with their GP or diabetes specialist team, as local formulary decisions may vary.

The medication is administered once weekly via subcutaneous injection using a pre-filled pen device, available in doses of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg, allowing for gradual dose escalation to optimise tolerability.

How Mounjaro Compares to Established Diabetes Medications

Mounjaro represents a significant advancement in the incretin-based therapy class, building upon the success of established GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy), dulaglutide (Trulicity), and liraglutide (Victoza). The key distinction lies in tirzepatide's dual mechanism: it activates both GIP and GLP-1 receptors, whereas traditional GLP-1 agonists target only the GLP-1 pathway. This dual action appears to enhance both glycaemic control and weight loss beyond what single-receptor agonists achieve.

In the SURPASS-2 head-to-head trial, Mounjaro demonstrated greater HbA1c reduction compared to semaglutide 1 mg, with the highest dose of tirzepatide (15 mg) achieving average HbA1c reductions of approximately 2.4% versus 1.9% with semaglutide at 40 weeks. Weight loss was similarly enhanced, with tirzepatide users losing an average of 11-12 kg compared to 6-7 kg with semaglutide at 40 weeks. These differences, whilst statistically significant, must be weighed against individual patient factors, tolerability, and cost considerations.

Compared to other established diabetes medications:

• Metformin – Mounjaro offers greater HbA1c reduction (2.0% vs 1.0-1.5%) and promotes weight loss rather than weight neutrality, but costs significantly more and requires injection rather than oral administration

• SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) – SGLT2 inhibitors have established cardiovascular and renal benefits from outcome trials; tirzepatide shows greater glycaemic control and weight loss but awaits definitive cardiovascular outcome data from SURPASS-CVOT

• Insulin – Mounjaro has a low risk of hypoglycaemia when used alone (risk increases when combined with insulin or sulphonylureas) and promotes weight loss, whereas insulin often causes weight gain; however, insulin remains essential for type 1 diabetes and advanced type 2 diabetes

The choice between Mounjaro and established therapies should be individualised, considering factors such as baseline HbA1c, BMI, cardiovascular risk, renal function, patient preference for injection versus oral therapy, and local formulary guidance. There is no universal superiority; rather, it represents an additional option within a comprehensive treatment algorithm.

What We've Learned Since Mounjaro's Launch

Since Mounjaro's approval in 2022, real-world experience has largely confirmed the efficacy and safety profile observed in clinical trials, whilst also revealing practical insights about its use in routine clinical practice. Post-marketing surveillance has reinforced that gastrointestinal adverse effects—particularly nausea, vomiting, and diarrhoea—remain the most common tolerability issues, typically occurring during dose escalation and often diminishing over time. Gradual dose titration, starting at 2.5 mg weekly and increasing every four weeks, helps minimise these effects.

Clinicians have gained experience managing patients who transition from other GLP-1 receptor agonists to tirzepatide, noting that prior tolerance of GLP-1 therapy generally predicts better tolerance of Mounjaro, though gastrointestinal effects may still occur. There is growing recognition that patient education about expected side effects, dietary modifications (smaller, more frequent meals), and realistic expectations about weight loss timelines improves adherence and satisfaction.

Important safety considerations that have been reinforced include:

• Monitoring for signs of pancreatitis (severe, persistent abdominal pain)

• Awareness of thyroid C-cell tumours observed in rodent studies (the risk in humans is unknown)

• Tirzepatide is not recommended in patients with severe gastrointestinal disease, including severe gastroparesis

• Potential for acute kidney injury secondary to dehydration from gastrointestinal effects

The ongoing SURPASS-CVOT trial, evaluating cardiovascular outcomes with tirzepatide, is expected to provide crucial data in 2025 regarding long-term cardiovascular safety and potential benefits. Additionally, tirzepatide has received MHRA authorisation for chronic weight management in obesity (under the brand name Mounjaro), though NICE appraisal will determine NHS access for this indication.

Patients currently taking Mounjaro should contact their GP if they experience:

• Severe, persistent abdominal pain that may radiate to the back

• Persistent vomiting preventing fluid intake

• Signs of dehydration (reduced urination, dizziness, dark urine)

• Symptoms of hypoglycaemia when used with insulin or sulphonylureas

Patients should report any suspected side effects to the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or via the Yellow Card app).

As Mounjaro approaches its third year on the market, the accumulating evidence continues to support its role as an effective option for type 2 diabetes management, particularly in patients requiring substantial glycaemic improvement and weight reduction. However, its relative novelty means long-term safety data beyond five years remain limited, and ongoing pharmacovigilance will continue to refine our understanding of its benefit-risk profile in diverse patient populations.

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