Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: $41,688 cost savings per patient, 0.506 QALYs gained

• Primary Outcome: Incremental cost-effectiveness ratio showing tirzepatide dominance

• Nnt Or Sensitivity: Per 1,000 patients: 70 fewer T2D cases, 10 fewer CVD cases with tirzepatide

• Confidence Interval: Not reported in abstract

Clinical Application

Requires access to both medications, lifestyle intervention support, and long-term monitoring Both medications available on PBS for obesity (tirzepatide recently listed). Cost-effectiveness may differ due to different healthcare costs and PBS pricing. RACGP obesity guidelines support pharmacotherapy as adjunct to lifestyle intervention. Adults with obesity or overweight with comorbidities, without established T2D

Abstract

PURPOSE: This study evaluated the cost-effectiveness (from the United States [US] societal perspective) of tirzepatide at its maximum-tolerated-dose (MTD) compared to semaglutide (MTD), both administered adjunct to a reduced-calorie diet and increased physical activity. The analysis focused on individuals with obesity (body mass index [BMI] ≥ 30 kg/m2), or overweight (BMI ≥27 to <30 kg/m2 + ≥1 obesity-related complication), using data from the head-to-head Phase-3 SURMOUNT-5 trial (patients without type 2 diabetes [T2D]). PATIENTS AND METHODS: This patient-level simulation modeling study assessed the cost and long-term clinical outcomes of tirzepatide (MTD) versus semaglutide (MTD), using data from the SURMOUNT-5 trial population. The modeled population were at risk of developing obesity-related complications including cardiovascular disease (CVD) and obstructive sleep apnea (OSA), amongst others. These outcomes were modeled using cardiometabolic parameters including weight, systolic blood pressure, high-density lipoprotein, glycated hemoglobin (HbA1c) and total cholesterol, by assessing their impact on healthcare and wider societal costs, quality of life, and mortality. Incremental cost-effectiveness ratios (ICERs; cost/quality-adjusted life year [QALY]) and incremental net health benefit (iNHBs) were calculated, and uncertainty was assessed through sensitivity and scenario analyses. RESULTS: Tirzepatide (MTD) was estimated to be less costly and more efficacious compared to semaglutide (MTD) with per patient cost savings of $41,688, 0.506 QALYs gained and positive iNHB of 0.784, indicating a net health benefit for tirzepatide. The model predicted that per 1,000 patients, 70 fewer patients will develop T2D, 10 fewer will develop CVD with tirzepatide (MTD) and patients spend 3.07 more years living with moderate/severe OSA when treated with semaglutide (MTD). CONCLUSION: Based on this simulation model, using head-to-head SURMOUNT-5 trial data, tirzepatide (MTD) had lower total costs and higher QALYs compared to semaglutide (MTD). This supports that tirzepatide (MTD) is a cost-effective treatment option for individuals with obesity or overweight compared to semaglutide (MTD). This study focused on evaluating the cost-effectiveness of two weight management drugs, tirzepatide and semaglutide, for adults in the US who are overweight or have obesity. Using data from the SURMOUNT-5 trial, the analysis showed that tirzepatide was more effective and less costly, providing better weight loss and health benefits compared to semaglutide.The findings revealed that for every 1,000 individuals treated with tirzepatide, there were 70 fewer cases of type 2 diabetes and 10 fewer cases of heart disease compared to those treated with semaglutide. Additionally, patients on semaglutide experienced a longer duration living with moderate or severe sleep apnea. The study highlighted that tirzepatide led to greater improvements in reducing weight and returning blood sugar levels to normal. Over a lifetime, tirzepatide was found to save $41,688 per patient and provide an additional 0.5 quality-adjusted life years (QALYs; a measure that helps compare how much different treatments improve both length and quality of life), emphasizing its advantages both financially and health-wise.Tirzepatide also demonstrated a reduction in absenteeism (when people are not at work because of illness or health problems) and presenteeism (when people are at work but not fully productive because they are unwell), meaning fewer days lost from work compared to semaglutide, thus highlighting productivity benefits. Overall, the research supports that tirzepatide offered a more cost-effective and beneficial treatment option for weight management in the US healthcare context compared to semaglutide.

References

1. 1.Johansson, E., Wilding, J. P. H., Upadhyay, N., van Hest, N., Kirk, M., Spaepen, E., Zimner-Rapuch, S., Annemans, L., & Bays, H. (2026). Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial. Journal of Medical Economics. https://doi.org/10.1080/13696998.2026.2646078