Abstract

Background: Tirzepatide, a novel GIP-GLP-1 receptor agonist therapy, has been shown to be beneficial for weight loss and reduction of cardiovascular disease (CVD) risk factors in adults with obesity in the SURMOUNT-1 trial. We estimated US population eligibility for tirzepatide and the impact on reduction of CVD events in US adults with obesity. Methods: We applied SURMOUNT-1 eligibility criteria (body mass index [BMI] > 30 kg/m 2 or BMI > 27 kg/m 2 with at least one risk factor or CVD, excluding diabetes) to US adults aged > 18 years in the US National Health and Nutrition Examination Survey (NHANES) 2015-2018 to estimate the US eligible population using NHANES sample weighting. Tirzepatide 15 mg group weight changes in the SURMOUNT-1 trial were applied to estimate the population impact on weight and obesity, and in those aged 30 to 74 years without prior CVD, the estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. The difference in the estimated risks with and without tirzepatide “treatment” multiplied by the eligible weighted population represented the estimated “preventable” CVD events. Results: We identified 4015 US adults weighted to an estimated population size of 93.4 million [M] (38% of the US adult population) who fit SURMOUNT-1 trial eligibility criteria, of which 51% were female and 89% were without prior CVD. Applying tirzepatide 15 mg SURMOUNT-1 treatment effects on weight loss resulted in an estimated 70.6% (65.9 M) and 56.7% (53.0 M) showing > 15% and > 20% weight reductions, respectively, translating to a 58.8% (55.0 M) reduction in obesity (BMI > 30 kg/m 2 ) prevalence and 36.4% (34.0 M) increase in normal weight (BMI <25 kg/m 2 ) prevalence among the eligible population. Among those without CVD, estimated 10-year CVD risks were 10.1% “before” and 7.8% “after” tirzepatide “treatment” reflecting a 2.3% absolute (and 23% relative) risk reduction (number needed to treat [NNT]=43) translating to an estimated 1.95 million preventable CVD events over 10 years. Conclusions: Tirzepatide treatment in eligible US adults may reduce obesity prevalence nearly 60% representing 55M adults and prevent up to 2M CVD events over 10 years, suggesting a dramatic impact on societal burden and healthcare costs in those with these conditions.

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