Tirzepatide is a first-in-class dual agonist at receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) for the treatment of T2D and obesity, with unprecedented efficacy for glycaemic control, reductions in body weight and improvements in blood pressure and lipid profile compared with placebo and GLP-1 receptor agonists. To date, clinical trials of tirzepatide have fulfilled the requirement by regulatory authorities of demonstrated cardiovascular safety in high-risk patients. Whether cardiovascular benefits will be found with dual GLP-1/GIP receptor agonists remains uncertain, and the contribution of GIP receptor activation to cardiovascular risk has not been established. Several ongoing large-scale cardiovascular outcome trials for tirzepatide will provide a clearer understanding of where tirzepatide should be positioned in the treatment of established atherosclerotic cardiovascular disease or in people at high risk, in relation to current standard-of-care cardioprotective agents and approaches.
Authors
Sumithran, Priya; Russell, Anthony W; Zoungas, Sophia