Obesity is a complicated chronic disease affecting over 40% of US adults. Tirzepatide and semaglutide are examples of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) that significantly reduce weight and improve cardiovascular health. However, access has been restricted due to high costs and shortages of medicine availability because of high demand. Â
Cost-effectiveness assessments showed conflicting results, with some studies finding certain medications are cost-effective while others are not. Previous clinical studies used outdated price estimates and trial-based data as well as real-world applicability. Hence, a reassessment was needed for a better understanding of the long-term health and economic impacts of anti-obesity medication on the U.S. population.
A recent study published in JAMA Health Forum assessed the cost-effectiveness and lifetime health benefits of four anti-obesity drugs (semaglutide, tirzepatide, phentermine-topiramate, and naltrexone-bupropion) combined with lifestyle modifications compared to lifestyle modification alone.
A validated dynamic and probabilistic Diabetes, Obesity, and Cardiovascular Disease Microsimulation (DOC-M) model was used for this long-term assessment. For this analysis, data were collected from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) consisting of 4823 individuals aged between 20 and 79 years and included the participants with body mass index (BMI) of ≥30 kg/m² and BMI of 27 to 29.9 kg/m²along with at least one comorbidity related to weight including hypertension, cardiovascular disease (CVD), dyslipidemia and diabetes. The lifestyle changes included a 500 kcal/d hypocaloric diet and weekly exercise, which involved at least 150 minutes of vigorous physical activity.
Outcomes like long-term cardiometabolic, treatment expenditures, non-treatment health care costs, productivity loss, health-related quality of life, quality-adjusted life-years (QALYs), and total costs were measured. Different analysis techniques were used, including multiple scenario analysis, subgroup analysis, and probabilistic sensitivity analysis. QALYs and future expenses were discounted by 3% annually.
A total of 126 million U.S. adults (mean age = 48±0.5 years, 51% female, mean BMI = 34.7±0.2 kg/m²) were eligible for this study. At least one weight-related comorbidity was present in 85% of participants.
Over a lifetime, results showed that tirzepatide could prevent 45,609 cases of obesity per 100,000 U.S. adults with a 95% uncertainty interval [UI] of 45,092-46,126, whereas semaglutide could prevent 32,087 cases with 95% UI of 31,292-32,882. Both tirzepatide and semaglutide would decrease the number of incident cases of diabetes by 20,854 (95% UI: 19,432-22,276) and 19,211(95% UI: 17,878-20,544) per 100,000 people, respectively. For every 100,000 U.S. individuals, tirzepatide would decrease 10,655 cases (95% UI: 10,124-11,186) of CVD, and semaglutide would decrease 8,263 cases (95% UI: 7,738-8,788).
Among all anti-obesity drugs, tirzepatide and semaglutide had additional QALY gains of 0.35 and 0.25, respectively. However, their incremental cost-effectiveness ratios were found to be $197Â 023/QALY for tirzepatide and $467Â 676/QALY for semaglutide. Additional price reduction of 30.5% for tirzepatide and 81.9% for semaglutide would be necessary to reach the $100,000/QALY threshold.
Naltrexone-bupropion was a cost-saving medication due to its low price and 89.1% probability of being cost-effective at $100 000/QALY than phentermine-topiramate medication, which had a 23.5%. The probability of tirzepatide and semaglutide was 0% for all QALY threshold ranges that were estimated at $ 100,000-$ 200,000/QALY.
In conclusion, this economic analysis highlights that tirzepatide and semaglutide medications were not cost-effective at present net costs, even though they provided significant long-term health effects. Reducing the net cost of new anti-obesity drugs is crucial to ensuring equitable access to these highly effective treatments.
Reference: Hwang JH, Laiteerapong N, Huang ES, Kim DD. Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults. JAMA Health Forum. 2025;6(3):e245586. doi:10.1001/jamahealthforum.2024.5586
