Cardiovascular Risk Reduction With Tirzepatide, a Dual GIP/GLP-1 Agonist, in Patients With Type 2 Diabetes Mellitus

Tirzepatide is the first dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GLP-1) receptor agonist to be approved for the treatment of diabetes mellitus. The SURPASS trials investigated the efficacy and safety of tirzepatide, both as monotherapy and as add-on therapy, in comparison with placebo, basal insulin, semaglutide, or dulaglutide in patients with type 2 diabetes. Tirzepatide at doses of 5 mg, 10 mg, or 15 mg produced significant reductions in hemoglobin A1c levels (-1.87% to -2.58%) and body weight (-6.2 to -12.9 kg) in patients with type 2 diabetes, without increasing the risk of serious hypoglycemia. Tirzepatide also improved lipid parameters and lowered blood pressure. Most of the observed adverse events were mild gastrointestinal symptoms, and the occurrence rate of these events was comparable to that associated with GLP-1 receptor agonists such as semaglutide (1 mg) or dulaglutide (0.75 mg). In this review, we summarize the pharmacodynamics and pharmacokinetics of tirzepatide, review the findings from the phase III SURPASS clinical trials, and discuss the anticipated beneficial effects of tirzepatide on the prevention and management of atherosclerosis and dyslipidemia in patients with type 2 diabetes mellitus.