Tirzepatide for Weight Management
Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide was approved for the treatment of obesity and for type 2 diabetes in the UK in late 2023 and will launch for both indications at the same time in February 2024. It has been available in the US for type 2 diabetes under the brand name Mounjaro® since 2022 and has been indicated for obesity and overweight under the brand name Zepbound® in the US since 2023. It is available as a solution for injection in prefilled pens and can only be obtained with a prescription. It is injected under the skin of the abdomen (belly), upper arm or thigh.
Unlike the GLP-1 receptor agonists (semaglutide and liraglutide), Mounjaro® acts as a receptor agonist for both GLP-1 and GIP, which means it stimulates both the GLP-1 and GIP receptors to enhance glucose control and regulate appetite. Therefore, tirzepatide is a dual GIP and GLP-1 receptor agonist1,2. Tirzepatide has greater affinity for the GIP receptor than for the GLP-1 receptor2 . It is a small molecule with a molecular weight of 4.8 kDa, for once-weekly subcutaneous administration1,2 .
Mounjaro is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with an initial Body Mass Index (BMI) of
Similar to the indication for liraglutide for weight management; for overweight patients with a BMI between 27 and 30kg/m2 , a weight related co-morbidity must occur before a patient can be prescribed Mounjaro® ‘on label’. The examples provided are not limiting and other weight related co-morbidities may be considered within label.
The starting dose of Mounjaro® is 2.5 mg once a week. After four weeks, this dose should be increased to 5 mg. If needed, the dose can be further increased by 2.5 mg increments every four weeks, up to a maximum of 15 mg once a week. Mounjaro® should be administered on the same day each week.
Clinical Trials for Weight Management: SURMOUNT-1 Clinical Study PDF can be found here
The key finding from the SURMOUNT-1 clinical study on tirzepatide which lead to the product gaining its licence for the treatment of Obesity is:
Safety Profile: The most common side effects with Mounjaro (which may affect more than 1 in 10 people) include problems with the digestive system, such as nausea (feeling sick), diarrhoea and vomiting. These were generally mild or moderate in severity and occurred more often when the dose of Mounjaro was changed.
Which is more effective – Wegovy® or Mounjaro®?
No head-to-head data with the same dosing regime is available, which would be required to provide conclusions on the comparison between Mounjaro® and Wegovy®.
Both semaglutide and tirzepatide are valuable treatment options, but the choice between them may depend on individual patient needs, preferences, and responses to treatment. It is important for healthcare providers to consider the specific clinical profile of each patient when selecting the most appropriate medication.
Future studies
The ongoing SURPASS-CVOT study will assess the cardiovascular safety of tirzepatide in Type 2 Diabetics and is due to be published in late 2024. The outline of the study can be found here. This study will be similar to the SELECT study for Wegovy®, however at this stage is only in Type 2 diabetics. This study will contribute to the increasing amount of data supporting the use of these pharmaceutical interventions for those who have a high risk of cardiovascular issues but have not as yet developed them.
A recent study published in February 2024 in the journal Hypertension (found here) showed that tirzepatide reduces blood pressure in adults classified as overweight. Patients taking 10mg or 15mg had average reductions of 10.6mmHG and 8.0mmHg respectively. These effects were evident during both day and night blood pressure measurements and rivals what is seen for many hypertension medications. More studies in this area can be anticipated.
References:
1. Willard FS et al. JCI Insight 2020;5:e140532;
2. Coskun T et al. Mol. Metab 2018;18:3–14
EMA. Mounjaro Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro
Clinical Trials.gov. A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT) Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04255433