Tirzepatide, Semaglutide Show Long-Term Benefits, But Are Not Cost-Effective

Although tirzepatide (Zepbound, Mounjaro) and semaglutide (Ozempic, Wegovy) show long-term benefits, investigators found that the drugs are not cost-effective at the current net prices, furthering the need to reduce the prices of the medication.¹

GLP-1 medications transformed the management of diabetes. Image Credit: Andreas Prott | stock.adobe.com

Glucagon-like peptide-1 (GLP-1) receptor agonists are being used to treat type 2 diabetes and obesity, with indications expanding into cardiovascular health and chronic kidney disease. Although tirzepatide and semaglutide are the most mentioned, dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and exenatide (Byetta) are also in the same class of medication. Investigators found robust evidence for GLP-1, such as reduced hemoglobin A_1c levels, weight loss, and improved cardiovascular outcomes. The class of medication transformed the management of diabetes, according to the authors of a StatPearls article.²

In another study published in Health Affairs Scholar, the authors stated that the medications show promise for the obesity pandemic, but the high price and potential impacts on long-term health care spending are still barriers for GLP-1 receptor agonists. There is limited access to coverage of GLP-1s, which can further expand health disparities, especially since obesity can disproportionately affect individuals from racial and ethnic minority populations and those with low socioeconomic status.³

In the current study, the authors stated that in some studies, semaglutide was cost-effective compared to no treatment, but other analyses show that semaglutide and tirzepatide were not cost-effective compared with lifestyle modifications due to the high cost. Therefore, the investigators evaluated the lifetime health effects and cost-effectiveness of tirzepatide, semaglutide, naltrexone-bupropion, or phentermine-topiramate combined with lifestyle modifications compared with lifestyle modifications alone. They used a model that estimated the probabilities of 5 health states and 4 cardiovascular disease events for individuals and included demographic characteristics, baseline health conditions, cardiometabolic risk factors, and population-level risk of the disease states.¹

Data from the 2017 to 2020 National Health and Nutrition Examination Survey, including 4823 individuals aged 20 to 79 years. Individuals included had a body mass index of 30 or greater (obesity) or had a BMI (body mass index) between 27 and 29.9 and at least 1 weight-related comorbidity (overweight). In each simulation, the patients received 1 of the 4 medications along with lifestyle modifications or the lifestyle modifications alone. Lifestyle medications were defined as a hypocaloric diet with a 500 kcal/d deficit and exercises of at least 150 minutes per week.¹

The individuals included were representative of 126 million US adults, with a mean age of 48 years and 51% being female. When compared with only lifestyle modifications, all 4 medications reduced the rates of obesity, diabetes, and cardiovascular disease and related deaths over 60 years. Tirzepatide and lifestyle modifications reduced the highest number of obesity, diabetes, and cardiovascular disease cases per 100,000 eligible individuals, according to the study authors. Naltrexone and bupropion had the smallest decrease across the 3 cases. For the secondary outcomes, tirzepatide and lifestyle modifications had the largest effects on first and second incident cases of cardiovascular disease and diabetes-related and cardiovascular-related deaths, followed by semaglutide, phentermine-topiramate, and naltrexone-bupropion.¹

For cost-effectiveness, tirzepatide and semaglutide showed long-term health care cost savings and the lowest levels of productivity loss due to improved health outcomes. However, the high cost of the medications offset the savings, the study authors said. Tirzepatide had the lowest mean per-person background health care expenditures, followed by semaglutide, at $154,028 and $160,974, respectively. Due to the high treatment cost, the incremental cost-effectiveness ratio was $197,023/quality-adjusted life-years (QALY) and 467,676 per QALY.¹

Investigators of the study also acknowledged considerations of alternatives for antiobesity medication, which included compounded GLP-1 receptor agonists, but limitations can include that safety and efficacy of the compounded treatments are unverified. “Future research should rigorously evaluate the safety, efficacy, and cost-effectiveness of these alternatives compared with treatments approved by the US Food and Drug Administration,” the study authors concluded.¹

References

1. 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

2. Latif W, Lambrinos KJ, Patel P, et al. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs) [Updated 2024 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572151/

3. Kim DD, Hwang JH, Fendrick AM. Balancing innovation and affordability in anti-obesity medications: the role of an alternative weight-maintenance program. Health Aff Sch. 2024;2(6):qxae055. Published 2024 May 2. doi:10.1093/haschl/qxae055