Glucagon-like peptide 1 (GLP-1) based therapy is an established treatment option 
for the management of type 2 diabetes mellitus (T2DM) and is recommended early 
in the treatment algorithm owing to glycaemic efficacy, weight reduction and 
favourable cardiovascular outcomes. Glucose-dependent insulinotropic polypeptide 
(GIP), on the other hand, was thought to have no potential as a glucose-lowering 
therapy because of observations showing no insulinotropic effect from 
supraphysiological infusion in people with T2DM. However, emerging evidence has 
illustrated that co-infusion of GLP-1 and GIP has a synergetic effect, resulting 
in significantly increased insulin response and glucagonostatic response, 
compared with separate administration of each hormone. These observations have 
led to the development of a dual GIP/GLP-1 receptor agonist, known as a 
'twincretin'. Tirzepatide is a novel dual GIP/GLP-1 receptor agonist formulated 
as a synthetic peptide containing 39 amino acids, based on the native GIP 
sequence. Pre-clinical trials and phase 1 and 2 clinical trials indicate that 
tirzepatide has potent glucose lowering and weight loss with adverse effects 
comparable to those of established GLP-1 receptor agonists. The long-term 
efficacy, safety and cardiovascular outcomes of tirzepatide will be investigated 
in the SURPASS phase 3 clinical trial programme. In this paper, we will review 
the pre-clinical and phase 1 and 2 trials for tirzepatide in the management of 
T2DM and give an overview of the SURPASS clinical trials.