Tirzepatide was linked to improved risk for atherosclerosis among patients with obesity.

Tirzepatide treatment is associated with a significant reduction in 10-year risk for atherosclerosis among individuals with obesity or overweight and without diabetes, according to study findings published in Diabetes, Obesity and Metabolism.

Findings from the phase 3, randomized clinical SURMOUNT-1 (ClinicalTrials.gov; Identifier: NCT04184622) trial supported the use of tripeptide for chronic weight management among patients with obesity. However, the effect of tirzepatide on long-term risk for atherosclerosis remains unknown.

To assess the relationship between tirzepatide and obesity-related cardiovascular complications, researchers conducted post-hoc analysis of the SURMOUNT-1 clinical trial using participant data from baseline up to week 72. Participants were randomized to receive either 5, 10, or 15 mg tirzepatide or placebo weekly as an adjunct to lifestyle intervention.

Inclusion criteria were adults with obesity or overweight without diabetes. The researchers excluded patients with a history of cardiovascular disease for this analysis.

Primary outcomes were changes in antihypertensive and antihyperlipidemic therapy, waist circumference, blood pressure, glycated hemoglobin, and fasting glucose. The researchers calculated the change in 10-year atherosclerosis risk using the American College of Cardiology and American Heart Association risk engine, which stratified risk scores according to:

• Low-risk (<5%);
• Borderline-risk (5-7.5%);
• Intermediate-risk (7.5-20%); and,
• High-risk (≥20%).

The study population included 2461 participants, of whom 622, 614, 616, and 609 were assigned to the placebo and tirzepatide 5 mg, 10 mg, and 15 mg groups, respectively. The mean age was 44.5 years (SD, 12.3) and the mean body mass index was 38.0 kg/m². Among the study population, 68.4% were women and 70.3% were White.

At baseline, the proportions of participants with low-risk, borderline-risk, intermediate-risk, and high-risk atherosclerosis risk scores were 80.4%, 8.6%, 10.0%, and 1.0%, respectively. Baseline median 10-year risk scores ranged between 1.5% and 1.6% and did not vary between treatment groups.

The researchers noted significantly greater reductions in atherosclerosis risk among the treatment groups compared with placebo. At week 72, the relative changes in predicted 10-year atherosclerosis risk were -16.4% (tirzepatide 5 mg), -23.5% (tirzepatide 10 mg) and -22.4% (tirzepatide 15 mg) compared with 12.7% (placebo; P <.001).

Among the subset of participants with baseline intermediate- and high-risk scores, the relative changes in atherosclerosis risk scores at week 72 were -10.3% (tirzepatide 5 mg), -20.6% (tirzepatide 10 mg), and -16.1% (tirzepatide 15 mg) compared with 6.4% (placebo; P <.05).

Compared with placebo, participants treated with tirzepatide had significantly improved odds of achieving reduced atherosclerosis risk at week 24 (odds ratio [OR], 2.2; 95% CI, 1.6-3.0; P <.001) and week 72 (OR, 2.4; 95% CI, 1.7-3.5; P <.001). Similarly, tirzepatide-treated participants with intermediate- and high-risk scores at baseline had significantly increased odds of achieving reduced atherosclerosis risk at week 24 (OR, 2.8; 95% CI, 1.4-5.6; P =.003) and week 72 (OR, 2.9; 95% CI, 1.3-6.2; P =.008).

Study limitations include the fact that the atherosclerosis risk engine was not developed or validated among populations of patients with obesity or overweight exclusively.

“[T]reatment with tirzepatide significantly reduced the 10-year predicted risk of [atherosclerosis] compared with placebo in people with obesity or overweight but without diabetes,” the researchers wrote. “The absolute reduction in risk was greater for participants with higher [atherosclerosis] risk at baseline.”