High Price of GLP-1 Agents Tip Cost-Benefit Scale Unfavorably

Despite substantial health benefits, two GLP-1 receptor agonists weren’t cost-effective at their current prices, according to an economic evaluation that compared four anti-obesity medications.

Net prices of tirzepatide (Mounjaro, Zepbound) and semaglutide (Ozempic, Wegovy) would have to drop by 30.5% and 81.9%, respectively, to reach the $100,000 per quality-adjusted life-year (QALY) threshold, reported researchers led by Jennifer Hwang, DO, of the University of Chicago, in JAMA Health Forum.

Even so, these GLP-1 agents have the potential to avert tens of thousands of cases of obesity, diabetes, and cardiovascular disease over a lifetime of use:

• Obesity: 45,609 with tirzepatide and 32,087 with semaglutide per 100,000 individuals
• Incident diabetes: 20,854 and 19,211, respectively
• Cardiovascular disease: 10,655 and 8,263

These “striking” findings underscore a “significant affordability challenge despite the clear clinical benefits,” Hwang told MedPage Today. “Obesity pharmacotherapy … can offer significant health benefits, but high costs limit access for many patients.”

“Prior studies have shown mixed results due to variations in assumptions and cost estimates,” she said. “By incorporating a broader range of health outcomes and the latest price data, we provide a more updated and nuanced picture of the trade-off between clinical benefits and economic feasibility.”

Compared with lifestyle modification alone, all four medications assessed in the study — including phentermine-topiramate (Qsymia) and naltrexone-bupropion (Contrave) — increased life expectancy and QALYs gained. Tirzepatide generated the most life-years gained per 100,000 eligible population, at 48,649, followed by semaglutide (35,634), phentermine-topiramate (20,153), and naltrexone-bupropion (11,406).

Tirzepatide and semaglutide were associated with larger QALY gains (incremental gains of 0.35 and 0.25 over lifestyle modification alone), greater long-term healthcare cost savings, and less productivity loss owing to improved health outcomes, “but the high costs of tirzepatide and semaglutide offset these savings,” the researchers noted.

“Compared with lifestyle modification alone, tirzepatide and lifestyle modification had the lowest mean per-person background healthcare expenditures at $154,028, followed by semaglutide and lifestyle modification at $160,974,” they pointed out. “However, due to their high treatment costs, the [incremental cost-effectiveness ratio] was $197,023/QALY gained for tirzepatide and lifestyle modification and was $467,676/QALY gained for semaglutide and lifestyle modification.”

Hwang said physicians must advocate for policies that improve affordability, whether through insurance coverage expansions, price negotiations, or alternative prescribing strategies, such as lower-dose maintenance regimens after initial weight loss. “Understanding the cost-effectiveness of these treatments can help us make more informed, patient-centered prescribing/treatment decisions,” she said.

“Obesity is a chronic disease that requires long-term management, and medication access should not be dictated solely by financial barriers,” Hwang added. “As new policies like the Inflation Reduction Act and the Treat and Reduce Obesity Act evolve, it is crucial for healthcare providers to stay engaged in discussions on equitable access to these life-changing treatments.”

Hwang’s group conducted their lifetime cost-effectiveness analysis in 2024 using the validated Diabetes, Obesity, Cardiovascular Disease Microsimulation model for U.S. adults. They included data from the 2017-2020 National Health and Nutrition Examination Survey of 4,823 individuals (representing 126 million eligible U.S. adults) ages 20 to 79 who would meet the following obesity clinical trial inclusion criteria: body mass index (BMI) of ≥30 or a BMI of 27-29.9 with at least one weight-related comorbidity.

Average age was 48 years, 51% were female, average baseline BMI was 34.7, and 85% had at least one weight-related comorbidity.

The researchers ran simulations where eligible adults received one of four anti-obesity medications — tirzepatide, semaglutide, phentermine-topiramate, or naltrexone-bupropion — paired with lifestyle modification or lifestyle modification alone. These simulations took into account projected long-term cardiometabolic outcomes, assumed weight loss in the first 2 years, and first year discontinuation due to adverse events.

SSR Health data were used to estimate net prices, which reflected rebates and discounts across Medicaid, the 340B drug pricing program, Medicare Part D, and commercial insurers. QALY estimates were computed using the U.S. health-related quality-of-life prediction model, which incorporated variables such as age, sex, race/ethnicity, and health conditions.

The current model did not include other weight-related comorbidities, such as osteoarthritis and obstructive sleep apnea, the latter of which tirzepatide was approved for in December.

The GLP-1 agent cost-benefit ratio could change in the future as additional health benefits are discovered and prices change. “Accounting for the long-term health benefits from reducing these comorbidities with anti-obesity medications might improve their cost-effectiveness,” Hwang’s group concluded.

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