Tirzepatide significantly reduces predicted risk of ASCVD among patients with obesity without diabetes

The results of the phase 3 trial reveal that tirzepatide treatment over 72 weeks significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes. The findings are published in the journal Diabetes, Obesity and Metabolism.

Obesity differs from person to person and requires an individualized, multifaceted approach. Several previous clinical recommendations have focused on lifestyle changes, including dietary modification and increased physical activity, as the first line of treatment, current clinical guidelines increasingly recognize the benefits of anti-obesity pharmacotherapy as an adjunct to lifestyle modification.

Dr Hankosky and team assessed the effect of tirzepatide on long-term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT-1.

Researchers conducted a post hoc analysis of SURMOUNT-1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m2 and at least one weight-related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed.

Researchers calculated a predicted 10-year ASCVD risk scores based on American College of Cardiology/American Heart Association risk engine at baseline, week 24, and week 72 in SURMOUNT-1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline.

The key findings of the study are

• Tirzepatide-treated groups demonstrated reductions in cardiometabolic variables over 72 weeks.

• In 2461 participants without a history of ASCVD, the baseline median risk score was low and did not differ across groups (1.5%–1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (−23.5% to −16.4%) than placebo (12.7%; P < 0.001).

• Relative change among participants with intermediate-to-high baseline risk was significantly greater for tirzepatide (P < 0.05).

• Intermediate-to-high-risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population.

In conclusion Dr Hankosky and team concluded that “Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.”

Reference: Emily R. Hankosky PhD, Hui Wang PhD, Lisa M. Neff MD, Hong Kan PhD, et al; Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis; 06 November 2023, Diab. Obs. Met.; DOI:  https://doi.org/10.1111/dom.15318.