Tirzepatide and Semaglutide Improve Weight Loss, Cardiovascular Conditions, but Deemed Too Expensive

Weight loss drugs like tirzepatide and semaglutide are growing in popularity and offer significant health benefits, but they are not cost-effective at their current prices, according to a new evaluation, placing economic burdens on patients with obesity in the US. | Image Credit: K KStock - stock.adobe.com

Tirzepatide (Zepbound; Eli Lilly) and semaglutide (Wegovy and Ozempic; Novo Nordisk), popular weight loss drugs that show significant health benefits for reduced rates of obesity, diabetes, and cardiovascular disease, are not cost-effective at their current prices, according to economic analysis results published in JAMA Health Forum.¹

Obesity affects more than two-fifths of US adults, which explains the growing popularity of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for obesity treatment. These drugs offer opportunities to mitigate the substantial health and economic burdens of the chronic disease. Increased public demand for GLP-1 RAs has led to supply shortages, and high costs have caused insurance companies to limit access.

Weight loss medications are often too expensive to afford out-of-pocket, typically marketed at an average price of $1000 per month.² Even with Eli Lilly’s recent self-pay alternative of a single-dose vial of tirzepatide at a 50% or greater discount, many Americans still cannot afford $5000 per year out-of-pocket. 

Researchers evaluated the lifetime health effects and cost-effectiveness of 4 antiobesity medications (tirzepatide, semaglutide, naltrexone-bupropion, phentermine-topiramate) combined with lifestyle modification vs lifestyle modification alone.¹ The investigation focused on analyzing cost-effectiveness to understand the health and economic implications of antiobesity medications for the US population. Researchers gathered the population data from the 2017 to 2020 National Health and Nutrition Examination Survey of 4823 individuals aged 20 to 79 years.

The survey of 126 million eligible US adults revealed a mean age of 48 years, with approximately 51% being women, an initial mean body mass index of 34.7, and 85% having at least 1 weight-related comorbidity. All 4 antiobesity medications, when combined with lifestyle modification, reduced the rates of obesity, diabetes, and cardiovascular disease, as well as related deaths, over the patients' lifetimes compared with lifestyle modification alone.

Tirzepatide combined with lifestyle modification reduced the highest number of obesity cases (45,609 per 100,000 eligible individuals), diabetes cases (20,854 per 100,000 eligible individuals), and cardiovascular disease cases (10,655 per 100,000 eligible individuals). Tirzepatide and lifestyle modification had the largest effects on reducing secondary outcomes followed by semaglutide, phentermine-topiramate, and naltrexone-bupropion, all with lifestyle modification.

Combining all 4 antiobesity medications with lifestyle modification increased patient life expectancy and quality-adjusted life-years (QALYs) to varying degrees compared with lifestyle modification alone. Tirzepatide and lifestyle modification generated 48,649 life-years gained per 100,000 eligible individuals, and semaglutide and lifestyle modification generated 35,634 life-years gained per 100,000 eligible individuals.

Furthermore, phentermine-topiramate and lifestyle modification generated 20,153 life-years gained per 100,000 eligible individuals, and naltrexone-bupropion and lifestyle modification generated 11,406 life-years gained per 100,000 eligible individuals.

Patients using tirzepatide or semaglutide, combined with lifestyle modification, achieved long-term health care cost savings and experienced the lowest levels of productivity loss due to improved health outcomes. However, the high costs of tirzepatide and semaglutide negated these savings. Tirzepatide combined with lifestyle modification resulted in the lowest mean per-person background health care expenditures, at $154,028, followed by semaglutide and lifestyle modification, at $160,974.

The incremental cost-effectiveness ratio (ICER) reached $197,023/QALY gained for tirzepatide and lifestyle modification, and $467,676/QALY gained for semaglutide with lifestyle modification. Naltrexone-bupropion and lifestyle modification offered cost savings due to lower treatment costs. Phentermine-topiramate and lifestyle modification showed an ICER of $85,229/QALY gained.

The combination of lifestyle modification with naltrexone-bupropion consistently yielded cost savings across all overweight and obesity categories compared with lifestyle modification alone, for all antiobesity medications.

The subgroup analysis showed that individuals with comorbidities demonstrated greater incremental gains in QALY, suggesting that these interventions could offer more benefits to those with existing weight-related conditions. Naltrexone-bupropion and lifestyle modification saved costs in both the group with comorbidities and the group without comorbidities, while phentermine-topiramate and lifestyle modification yielded the lowest ICER of $110,600/QALY gained in the group with comorbidities.

Uncertainty regarding long-term real-world clinical effectiveness, adverse event rates, adherence, and net prices of antiobesity medications limited the researchers. The model might overestimate the benefits by projecting short-term clinical trial effects over a lifetime and assuming concurrent lifestyle modification. Differences in pricing structures introduce variability in cost estimates. The current microsimulation model omits diabetes-related microvascular complications but captures these effects indirectly through diabetes-related disutility and costs. The model also excluded other weight-related comorbidities like osteoarthritis and obstructive sleep apnea.

“Efforts to reduce the net prices of new antiobesity medications are essential to ensure equitable access to highly effective antiobesity medications,” the study authors concluded.

References

1. Hwang JH, Laiteerapong N, Huang ES, Kim DD. Lifetime health effects and cost-effectiveness of tirzepatide and semaglutide. JAMA Health Forum. 2025;6(3):e245586. doi:10.1001/jamahealthforum.2024.5586
2. Shao WL. Contributor: how can the US health care system affordably and fairly expand GLP-1 access for the millions of people who need it? AJMC^®. March 5, 2025. Accessed March 14, 2025. https://www.ajmc.com/view/contributor-how-can-the-us-health-care-system-affordably-and-fairly-expand-glp-1-access-for-the-millions-of-people-who-need-it-