Tirzepatide is a new drug for the treatment of type 2 diabetes mellitus (T2DM). While it is not yet available in Australia, it has recently gained Therapeutic Goods Administration (TGA) approval for adults with insufficiently controlled T2DM as an adjunct to diet and exercise, where monotherapy with metformin alone has not been tolerated or contraindicated, or in addition to other pharmacotherapies for the treatment of T2DM (1). Though not yet TGA approved for the indication of obesity, tirzepatide also offers promising outcomes in substantially reducing body weight.
It is a unique and “first in its class” medication as it is both a glucagon-like peptide–1 (GLP-1) receptor agonist, as well as a long-acting glucose-dependent insulinotropic peptide (GIP) receptor agonist. Its action on the GLP-1 receptor stimulates insulin secretion in hyperglycaemic states, suppresses glucagon secretion, delays gastric emptying and decreases appetite. GIP receptors are widespread in adipose tissue and also have a role in increasing insulin sensitivity. Thus this dual mechanism functioning on both the GLP-1 and GIP incretins significantly reduces glycaemic levels and improves insulin sensitivity, whilst reducing body weight and improving lipid metabolism. Its C20 fatty-diacid moiety, which can bind to albumin, prolongs its half-life, enabling it to be dosed once a week via subcutaneous injection.
The pre-filled subcutaneous pen is presented in multiple different strengths, as the starting dose is 2.5mg once weekly and increasing to 5mg once weekly after four weeks. The dose can be increased in further 2.5mg increments after a minimum of four weeks, with the recommended maintenance doses being either 5mg, 10mg or 15mg, with the maximum dose being 15mg once weekly. Common side effects of tirzepatide are comparable to other GLP-1 agonists and include gastrointestinal side effects such as nausea, vomiting and diarrhoea, and the incidence of hypoglycaemia appears to be low.
Compared to semaglutide, which is currently on the market, studies have shown that tirzepatide has significantly superior therapeutic efficacy. A higher percentage of those using tirzepatide reached the glycated haemoglobin (HbA1c) target level of less than 7% compared to those on semaglutide, and the patients who received tirzepatide 15mg attained almost twice the weight loss of those who received semaglutide 1mg.
Thus, tirzepatide is an emerging and promising option for those with T2DM and obesity, showing superior effects compared to semaglutide.
- Australian prescription medicine decision summaries [Internet]. ACT Australia: Australian Government Department of Health and Aged Care, Therapeutic Goods Administration; 2023. Mounjaro; 2023 Jan 12 [cited 2023 Jan 18].
- Chavda VP, Ajabiya J, Teli D, Bojarska J, Apostolopoulos. Tirzepatide, a new era of dual-targeted treatment for diabetes and obesity: a mini-review. Molecules. 2022; 27 (13): 4315.
- Frias JP Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021; (385): 503-15.
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022; (387): 205-16.
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