by Justin Jackson , Medical Xpress

Credit: Unsplash/CC0 Public Domain

University of Chicago researchers assessed the long-term health outcomes and cost-effectiveness of four antiobesity medications compared to lifestyle modification alone. Results indicate that tirzepatide and semaglutide provide substantial health benefits, including reductions in obesity, diabetes, and cardiovascular disease cases. However, high treatment costs can render these medications economically inefficient under current pricing.

Naltrexone-bupropion emerged as the most cost-effective intervention, while phentermine-topiramate demonstrated moderate economic viability. Findings suggest that reducing the net prices of new antiobesity medications is necessary to improve accessibility.

Obesity affects more than 40% of U.S. adults and is associated with significant health and economic burdens. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide and tirzepatide have demonstrated effectiveness in promoting weight loss and reducing cardiometabolic risks. Increased demand has resulted in supply shortages, while high costs have prompted restrictive insurance coverage policies.

Previous studies evaluating the economic value of these medications have produced conflicting results. Some analyses identified semaglutide as cost-effective compared to no treatment, whereas others concluded that tirzepatide and semaglutide were not cost-effective relative to lifestyle modification alone.

Inconsistencies in prior findings stemmed in part from reliance on clinical trial populations and pricing estimates rather than real-world data.

In the study, “Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults,” published in JAMA Health Forum, researchers conducted a lifetime cost-effectiveness analysis to assess the economic viability of antiobesity medications combined with lifestyle modification versus lifestyle modification alone.

The validated Diabetes, Obesity, Cardiovascular Disease Microsimulation Model (DOC-M) was employed to forecast long-term outcomes, including quality-adjusted life-years (QALYs), health care costs, and disease prevalence.

Data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) were used, comprising 4,823 individuals aged 20 to 79 years, representing approximately 126 million eligible U.S. adults.

Participants met clinical trial criteria for antiobesity medications based on body mass index (BMI) and the presence of at least one weight-related comorbidity. Researchers applied individual-level simulations with probabilistic sensitivity analyses and subgroup assessments to account for BMI classifications, presence of comorbidities, and treatment discontinuation rates.

Each intervention included either lifestyle modification alone or lifestyle modification combined with one of four medications: naltrexone-bupropion, phentermine-topiramate, semaglutide, or tirzepatide. Lifestyle modification consisted of dietary changes and physical activity.

Researchers estimated treatment effects on weight reduction, cardiovascular risk factors, adverse events, and treatment discontinuation rates based on clinical trial data. Costs were adjusted to 2023 U.S. dollars, incorporating health-related expenditures, productivity loss, and background health care costs.

Tirzepatide prevented 45,609 cases of obesity per 100,000 individuals, the highest reduction among all interventions. Diabetes cases decreased by 20,854 per 100,000 individuals, while cardiovascular disease cases declined by 10,655 per 100,000 individuals.

Semaglutide showed a lower, yet significant, impact, preventing 32,087 obesity cases, 19,211 diabetes cases, and 8,263 cardiovascular disease cases per 100,000 individuals. Life-years and QALYs gained were highest for tirzepatide (0.50 life-years, 0.35 QALYs) and semaglutide (0.35 life-years, 0.25 QALYs).

Cost-effectiveness evaluations determined that naltrexone-bupropion was cost-saving, with an 89.1% probability of being cost-effective at the $100,000/QALY threshold. Phentermine-topiramate demonstrated a 23.5% probability of cost-effectiveness at the same benchmark.

Tirzepatide and semaglutide were deemed not cost-effective at current pricing, with incremental cost-effectiveness ratios (ICERs) of $197,023/QALY and $467,676/QALY, respectively. To achieve cost-effectiveness under the $100,000/QALY standard, price reductions of 30.5% for tirzepatide and 81.9% for semaglutide would be required.

Subgroup analyses indicated greater QALY gains among individuals with pre-existing comorbidities, suggesting that antiobesity medications may provide the most value for those at higher health risk. Sensitivity analyses reinforced the findings, with probabilistic simulations showing that tirzepatide and semaglutide remained economically inefficient across all cost-effectiveness thresholds examined.

Analysis determined that while tirzepatide and semaglutide offer significant health improvements, their high prices limit cost-effectiveness. Generic alternatives and alternative weight maintenance approaches, such as structured lifestyle interventions (dietary modifications, increased physical activity, and behavioral support) or lower-dose GLP-1 RAs, may provide additional cost-saving strategies.

More information: Jennifer H. Hwang et al, Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults, JAMA Health Forum (2025). DOI: 10.1001/jamahealthforum.2024.5586

Journal information:JAMA Health Forum

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