Semaglutide and Tirzepatide Use and Reduction of Cardiovascular Risks in Adults with Overweight and Obesity

Abstract

Background: Obesity is a prevalent, growing health concern in the United States, affecting over 42% of adults and contributing significantly to the burden of cardiovascular disease (CVD). Recently, approved anti-obesity medications (AOMs) such as semaglutide (Wegovy) and tirzepatide (Zepbound) have emerged as potential interventions to reduce weight and potentially lower cardiovascular risk among individuals with obesity. Aim: To analyze the impact of AOM on cardiovascular risk among US patients with obesity. Methods: Utilizing Kythera data, we conducted a retrospective cohort study from November 2022 to June 2024. Patients with obesity and AOM use were identified based on diagnosis claims and prescription claims for tirzepatide or semaglutide (identification period: Nov. 1, 2023–Dec. 31, 2023) with 6 months of follow-up to measure CVD risk. Exclusions included patients with pre-existing CVD and prior AOM use. Cox regression and multivariable analyses adjusted for comorbidities and sociodemographic factors were employed to assess the risk of cardiovascular events, with additional analyses comparing outcomes between tirzepatide and semaglutide users. Results: We identified 22,620 patients with obesity and AOM use and 84,427 patients with obesity without AOM use. Significant differences were observed in the proportion of patients with an Elixhauser Index Score ≥2, comprising 61.97% in the AOM cohort versus 13.50% in the non-AOM cohort (standardized difference = 1.2868). The AOM cohort demonstrated significantly lower incidence of cardiovascular events (1.77%) than non-AOM users (12.17%, p<0.0001). Adjusted analyses confirmed that AOM use was associated with a substantially reduced risk of CVD (hazard ratio=0.37, p<0.0001). Differences in specific cardiovascular outcomes between tirzepatide and semaglutide users were observed, with semaglutide users showing a higher hazard of CVD than tirzepatide users (hazard ratio=1.53, p=0.0215). Conclusions: Use of AOM was associated with a significantly lower risk-adjusted likelihood of cardiovascular events than non-use, highlighting these medications as promising interventions in obesity management.