Eli Lilly and Company has granted marketing authorisation (MA) by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for Mounjaro (tirzepatide), a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist, for weight management, including weight loss and weight maintenance, as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial BMI of ≥30 kg/m2 (obesity) or ≥ 27 kg/m2 to < 30kg/m2 (overweight) in the presence of at least one weight-related co-morbidity (e.g. hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease, prediabetes, or type 2 diabetes).
Tirzepatide is the first GIP and GLP-1 receptor agonist to receive MHRA marketing authorisation for weight management in adults in Great Britain. Tirzepatide currently has marketing authorisation in Great Britain for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise.
“Obesity is a complex, chronic disease that significantly negatively impacts people’s health, quality of life and life expectancy. Tackling obesity requires a holistic approach including prevention strategies, and for those already affected by obesity, clinical services and effective treatment options,” said Professor Rachel Batterham, Senior Vice President for International Medical Affairs at Lilly. “We’re delighted that tirzepatide has been authorised in Great Britain. Tirzepatide is a new class of medication that can offer eligible people living with obesity another treatment option and potentially reduce the economic impact of obesity, which is estimated to cost the NHS £6.1 billion annually.”
This authorisation is based on results from the phase 3 SURMOUNT-1 and SURMOUNT-2 clinical trials, which both met their co-primary endpoints of demonstrating that tirzepatide 10mg and 15mg achieved superior mean percent change in body weight from baseline and greater percentage of participants achieving body weight reductions of at least 5% compared to placebo.
SURMOUNT-1 studied adults with obesity or overweight without diabetes and included a total of 2539 participants. SURMOUNT-2 evaluated adults with obesity or overweight and type 2 diabetes and included a total of 938 participants.
All participants treated with tirzepatide started the study at a dose of 2.5 mg once-weekly for 4 weeks. Then the dose of tirzepatide was increased by 2.5 mg every 4 weeks until they reached their assigned dose. In SURMOUNT-1 the dose of tirzepatide or matching placebo was escalated to 5 mg, 10 mg, or 15 mg subcutaneously once-weekly during a 20-week period followed by the maintenance period. In SURMOUNT-2, the dose of tirzepatide or matching placebo was escalated to 10 mg or 15 mg subcutaneously once-weekly during a 20-week period followed by the maintenance period.
In SURMOUNT-1, participants taking tirzepatide achieved average weight reductions of 16.0% (16.1 kg) on 5 mg once-weekly, 21.4% (22.2 kg) on 10 mg once-weekly and 22.5% (23.6 kg) on 15 mg once-weekly, compared to placebo (2.4%, 2.4 kg). Additionally, 89.4% (5 mg), 96.2% (10 mg) and 96.3% (15 mg) of people taking tirzepatide achieved at least 5% body weight reduction compared to 27.9% of those taking placebo.
In SURMOUNT-2, participants taking tirzepatide achieved average weight reductions of 13.4% (13.5 kg) on 10 mg once-weekly and 15.7% (15.6 kg) on 15 mg once-weekly compared to placebo (3.3%, 3.2 kg). Additionally, 81.6% (10 mg) and 86.4% (15 mg) of people taking tirzepatide achieved at least 5% body weight reduction compared to 30.6% of those taking placebo.
The overall safety profile of tirzepatide was consistent with previously reported SURPASS trials (SURPASS 1-5 were five global randomised, controlled, phase 3 studies evaluating the safety and efficacy of tirzepatide in patients with type 2 diabetes) and similar to other incretin-based therapies for the treatment of obesity.iv The most commonly reported adverse events were nausea, diarrhoea, vomiting and constipation and were generally mild to moderate in severity, usually occurring during the dose-escalation period.
The FDA recently approved tirzepatide for chronic weight management and will be marketed under the tradename Zepbound.