Del Prato S, Kahn SE, Pavo I, et al. - Treatment with tirzepatide (novel dual GIP and GLP-1 receptor agonist) conferred a greater and clinically meaningful glycated hemoglobin (HbA _1c ) reduction than insulin glargine, along with a lower incidence of hypoglycemia at week 52, in individuals with type 2 diabetes and elevated cardiovascular risk. No excess cardiovascular risk was noted with tirzepatide treatment.

• This open-label, parallel-group, phase 3 study included 2,002 adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications.

• Patients were randomized to receive tirzepatide or glargine; 1,995 were included in the modified intention-to-treat population.

• Tirzepatide led to mean HbA _1c changes at 52 weeks: −2·43% (SD 0·05) with 10 mg and −2·58% (0·05) with 15 mg, vs −1·44% (0·03) with glargine.

• The estimated treatment difference compared with glargine was −0·99% and −1·14% for tirzepatide 10 mg and 15 mg, respectively, and the non-inferiority margin of 0·3% was met for both doses.

• Tirzepatide was associated with a lower % of participants with hypoglycemia (6–9%) vs glargine (19%).

• No increase in adjudicated major adverse cardiovascular events-4 events (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina) resulted from tirzepatide vs glargine (hazard ratio 0·74), and 60 deaths (n=25 [3%] tirzepatide; n=35 [4%] glargine) were reported.