OBJECTIVES: Obesity is a prevalent and 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 Zepbound and Wegovy have emerged as potential interventions to reduce weight and potentially lower CVD risk among individuals with obesity. This study aimed to analyze the impact of AOM on the risk of CVD 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 claim(s) for Zepbound or Wegovy (identification period: 11/1/2023-12/31/2023) 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 Zepbound and Wegovy 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 Elixhauser Index Score ≥2, comprising 61.97% in the AOM cohort versus 13.50% in the non-AOM cohort (std. diff=1.2868). AOM users 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 [HR]=0.37, p<0.0001). Differences in specific cardiovascular outcomes between Zepbound and Wegovy users were observed, with Wegovy users showing a higher hazard of CVD than Zepbound users (HR=1.53, p=0.0215).

CONCLUSIONS: AOM use was associated with a significantly lower risk-adjusted likelihood of cardiovascular events than non-use, highlighting these medications as promising interventions in obesity management.