GLP-1 RECEPTOR AGONISTS — The injectable GLP-1 receptor agonists semaglutide (Ozempic), dulaglutide (Trulicity), and liraglutide (Victoza) and oral semaglutide (Rybelsus) are also approved for cardiovascular risk reduction in patients with type 2 diabetes. These drugs have reduced the risk of MACE by up to 20%.4 

A CLINICAL STUDY — FDA approval of tirzepatide for the new indication was based on the results of a double-blind trial (SURPASS-CVOT) in 13,299 patients ≥40 years old with inadequately-controlled type 2 diabetes and established ASCVD. Patients were randomized to receive tirzepatide titrated to 15 mg (or the maximum tolerated dose) or dulaglutide 1.5 mg injected subcutaneously once weekly in addition to standard care (other glucose-lowering and cardiovascular-risk reducing drugs). At baseline, about 30% of patients were taking a sodium-glucose cotransporter 2 (SGLT2 inhibitor; canagliflozin and empagliflozin have been shown to reduce the risk of MACE in patients with type 2 diabetes and ASCVD). After a median follow-up of 4 years, the incidence of MACE (a composite of nonfatal myocardial infarction, nonfatal stroke, or cardio-vascular death) with tirzepatide in the intent-to-treat population was noninferior to that with dulaglutide (12.2% vs 13.1%; HR 0.92, 95% CI 0.83-1.01). The incidences of all-cause mortality (8.6% vs 10.2), myocardial infarction (4.7% vs 5.4%), nonfatal stroke (3.5% vs 3.8%), and cardiovascular death (5.6% vs 6.2%) were lower with tirzepatide than with dulaglutide, but the differences were not statistically signifi cant. GI adverse effects were more common with tirzepatide than with dulaglutide.5

DOSAGE, ADMINSTRATION, AND COST — The recommended starting dosage of tirzepatide for patients with type 2 diabetes is 2.5 mg injected subcutaneously once weekly in the abdomen, thigh, or upper arm. After 4 weeks, the dose should be increased to 5 mg and then further increased in 2.5-mg increments every 4 weeks to 15 mg once weekly (maximum 10 mg in children ≤9 years old). A 28-day supply of Mounjaro 15 mg costs about $1112.6

CONCLUSION — Addition of the injectable GIP/GLP-1 receptor agonist tirzepatide (Mounjaro) to standard treatment reduces the risk of MACE in adults with type 2 diabetes and atherosclerotic cardiovascular disease.