The rising prevalence of obesity and its associated health burdens have spurred advancements in pharmaceutical interventions for weight management. Medications like semaglutide and tirzepatide, known by brand names such as Ozempic, Wegovy, Zepbound, and Mounjaro, which target glucagon-like peptide-1 (GLP-1) receptors, have emerged as promising treatments for both diabetes and obesity. These GLP-1 receptor agonists (GLP-1 RAs) mimic hormones that regulate hunger and satiety, helping individuals feel full sooner and eat less, leading to clinically relevant weight loss. However, the long-term cost-effectiveness of these therapies remains a critical consideration for healthcare systems, payers, and patients.
Understanding Cost-Effectiveness Analysis
Cost-effectiveness analysis (CEA) is a standardized approach for comparing the value of new antiobesity medications. It evaluates the incremental cost-effectiveness ratio (ICER), which represents the additional cost divided by the additional health benefit, often measured in quality-adjusted life years (QALYs). A QALY quantifies the number of life years gained and the health-related quality of life based on a health intervention. For a health care intervention to be considered cost-effective, the ICER must be below a certain threshold, which represents the amount a payer (i.e., insurers or government programs such as Medicaid and Medicare) is willing to pay per QALY. A commonly accepted threshold among payers for cost-effectiveness is $100,000 per QALY.
Elena Losina, PhD, codirector of the Orthopedics and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital, notes that there is no commonly accepted willingness-to-pay or cost-effectiveness ratio in the United States. Different payers have different cost-effectiveness thresholds, influencing their preferred strategies.
Cost-Effectiveness of GLP-1 RAs Compared to Other Interventions
A recent study published in the Annals of Internal Medicine found that the GLP-1 RA tirzepatide was more cost-effective than semaglutide when treating patients with knee osteoarthritis and obesity. Anti-obesity medications have been shown to provide substantial pain relief for patients with obesity and knee osteoarthritis. The weight loss helped relieve patients of pain, slowed cartilage loss in those with knee osteoarthritis, and may have also had anti-inflammatory and immunomodulatory benefits.
However, GLP-1 RA usage is often long-term, and over time the cumulative costs have the potential to outweigh health benefits, thus disproportionately affecting marginalized communities. The study assessed the cost-effectiveness based on a lifetime quality-adjusted life-year (QALY) threshold that quantifies the number of life years gained and the health-related quality of life based on a health intervention like GLP-1 RAs.
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Nonpharmacologic interventions like diet and exercise had a lower QALY, ranging from $25,400 to $57,400, which indicates they provide good value even in a setting with limited health care benefits. Other weight loss interventions like tirzepatide and bariatric surgery had higher thresholds at $57,400 and $30,700, respectively, meaning they are considered worthwhile investments since health care systems are more willing to allocate larger sums per QALY gained.
While tirzepatide was seen to be more cost-effective than semaglutide, bariatric surgery, which includes gastric bypass and laparoscopy, showed a significantly lower ICER of $20,600 per QALY. Losina explained that bariatric surgery involves an upfront cost, but patients experience benefits for a long period, making it a cost-effective option for eligible and willing patients.
Semaglutide: A Detailed Cost-Effectiveness Analysis
Given the rising prevalence and profound economic burden associated with obesity and the evolving landscape of treatment options for weight management, comprehensive economic evaluations are crucial to inform decision-making for payers.
A cohort Markov model was constructed to compare semaglutide 2.4 mg with the following comparators: no treatment, diet and exercise (D&E), and 3 branded AOMs (liraglutide 3 mg, phentermine-topiramate, and naltrexone-bupropion). All AOMs, including semaglutide 2.4 mg, were assumed to be taken in conjunction with D&E. Changes in BMI, blood pressure, cholesterol level, experience of acute and chronic obesity-related complications, costs, and quality-adjusted life years (QALYs) were simulated over 30 years based on pivotal trials of the AOMs and other relevant literature. Drug and health care prices reflect 2021 standardized values. Cost-effectiveness was examined with a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. In the base-case analysis, treatment with semaglutide 2.4 mg was estimated to improve QALYs by 0.138 to 0.925 and incur higher costs by $3,254 to $25,086 over the 30-year time horizon vs comparators. Semaglutide 2.4 mg is cost-effective against all comparators at the prespecified WTP threshold, with the incremental cost per QALY gained ranging from $23,556 to $144,296 per QALY gained.
A cohort Markov model (Figure 1) was developed in Microsoft Excel to estimate the cost-effectiveness of semaglutide 2.4 mg vs comparators in patients with obesity and overweight from a US third-party payer perspective. The model design for the current study was informed by a review of prior health technology assessment submissions and published economic evaluations for the management of obesity and overweight. Comparators considered in the model included no treatment, D&E alone, and branded AOMs that are standard-of-care for long-term weight management (ie, liraglutide 3 mg, phentermine-topiramate, and naltrexonebupropion). AOMs that have been withdrawn from the US market were not included in the analysis. All AOMs, including semaglutide 2.4 mg, are used in conjunction with D&E. Patients’ physiological parameters, obesity complications, health care costs, and utility were simulated over 30 years, which allows the model to capture outcomes along patients’ disease course from treatment initiation (at age of 46 years based on STEP 1 trial data) to reaching stable weight (approximately age 65-70 years). A cycle length of 3 months was applied in the first year, allowing for more accurate representation of treatment effects immediately following treatment initiation. Annual cycles were applied after the first year. Half-cycle correction was applied to estimate occurrence of state transitions in the middle of each cycle.
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Treatment with semaglutide 2.4 mg was estimated to be cost-effective against the current standard of care, D&E, with an ICER of $122,549 given improved QALYs of 0.181 and additional costs of $22,138 over a 30-year horizon. Across all scenarios evaluated, the ICER for semaglutide 2.4 mg ranged from $30,540 to $253,206 compared with D&E. The model was most sensitive to maximum treatment duration and time horizon, followed by regimen after treatment discontinuation, weight-rebound rate, and semaglutide 2.4 mg efficacy on BMI.
Of note, if all patients discontinued D&E, in addition to AOMs, after the 2-year maximum treatment duration, ICERs ranged from $7,287 (vs liraglutide 3 mg) to $51,025 (vs phentermine-topiramate). The ICERs for the comparisons with liraglutide 3 mg and no treatment were consistently below the $150,000/QALY WTP threshold over a 30-year horizon under all scenarios examined in the DSA. Notably, semaglutide 2.4 mg was estimated to be particularly cost-effective compared with D&E, no treatment, and other AOMs in the subgroup of patients with obesity class III (ICERs ranged from $8,094 for liraglutide 3 mg to $85,024 for phentermine-topiramate).
Tirzepatide and Semaglutide: A Comparative Analysis of Lifetime Health Effects and Cost-Effectiveness
Table 3. These results support the need for ongoing efforts to further reduce the net prices of new antiobesity medications to ensure equitable access to these highly effective medications. Newer antiobesity medications lead to greater weight loss and lower cardiometabolic risks. A lifetime cost-effectiveness analysis was conducted in 2024 using the validated Diabetes, Obesity, Cardiovascular Disease Microsimulation model for US adults. Data were included from the 2017-2020 National Health and Nutrition Examination Survey of 4823 individuals (representing 126 million eligible US adults) aged 20 to 79 years who would meet clinical trial inclusion criteria for antiobesity medications. Individual-level simulations projected long-term cardiometabolic outcomes, quality-adjusted life-years (QALYs), and health care expenditures. Probabilistic sensitivity analyses, subgroup analyses (across body mass index [BMI] categories [≥30 or ≥27 and at least 1 weight-related comorbidity], presence of comorbidities), and multiple scenario analyses (varying treatment discontinuation rates, value-based pricing benchmarks) were conducted. Among the 126 million eligible US adults, the mean age was 48 (SE, 0.5) years; 51% were female; and the initial mean BMI was 34.7 (SE, 0.2); and 85% had at least 1 weight-related comorbidity. Over a lifetime, tirzepatide would avert 45 609 obesity cases (95% uncertainty interval [UI], 45 092-46 126) per 100 000 individuals and semaglutide would avert 32 087 cases (95% UI, 31 292-32 882) per 100 000 individuals. Tirzepatide would reduce 20 854 incident cases of diabetes (95% UI, 19 432-22 276) per 100 000 individuals and semaglutide would reduce 19 211 cases (95% UI, 17 878-20 544) per 100 000 individuals. Tirzepatide would reduce 10 655 cardiovascular disease cases (95% UI, 10 124-11 186) per 100 000 individuals and semaglutide would reduce 8263 cases (95% UI, 7738-8788) per 100 000 individuals. Despite the largest incremental QALY gains of 0.35 for tirzepatide and 0.25 for semaglutide among all antiobesity medications, the incremental cost-effectiveness ratios were $197 023/QALY and 467 676/QALY, respectively. To reach the $100 000/QALY threshold, their prices would require additional discounts by 30.5% for tirzepatide and 81.9% for semaglutide from their current net prices. Naltrexone-bupropion was cost saving due to its lower cost and had an 89.1% probability of being cost-effective at $100 000/QALY, whereas phentermine-topiramate had a 23.5% probability of being cost-effective at $100 000/QALY. This economic evaluation found that although tirzepatide and semaglutide offered substantial long-term health benefits, they were not cost-effective at current net prices.
Factors Influencing the Cost-Effectiveness of GLP-1 RAs
Treatment Duration and Time Horizon
ICERs of semaglutide 2.4 mg vs comparators increased over longer treatment durations in part because of the higher drug cost incurred in the semaglutide 2.4 mg arm and higher treatment persistence compared with other AOMs. ICERs also increased with a 5-year time horizon analysis, suggesting that a short-term model may not capture the full and long-term benefits of semaglutide 2.4 mg treatment. Indeed, given that obesity is a complex and chronic disease associated with various long-term comorbidities, a shorter-term time horizon is insufficient to capture the effects of obesity treatments on the risk of chronic comorbidities in the long term and the associated impact on health care costs and quality of life. Thus, a 30-year time horizon was used to cover all relevant health outcomes and costs of obesity intervention. Additionally, since natural weight gain typically levels off at approximately 65-70 years, a 30-year horizon is sufficient to cover the time between treatment initiation (at age 46 years based on the STEP 1 trial) and this natural weight-gain plateau.
Net Prices and Discounts
The high costs of GLP-1 RAs have led insurance companies to limit access. To reach the $100,000/QALY threshold, their prices would require additional discounts by 30.5% for tirzepatide and 81.9% for semaglutide from their current net prices. Efforts to reduce the net prices of new antiobesity medications are essential to ensure equitable access to highly effective antiobesity medications.
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Patient Selection and Treatment Strategies
These drugs aren’t equally effective for everyone. Some patients respond incredibly well, and others don’t. Refining clinical guidelines for prescribing GLP-1 drugs more selectively can help reduce costs significantly. If we don’t have to keep everyone on these drugs forever, we can reduce costs significantly.
GLP-1 RAs in the Broader Context of Obesity Treatment
Prevention and management of obesity and overweight are often challenging, as the etiology is complex and multifactorial, involving genetic, physiological, behavioral, and environmental factors. Emerging treatment options now allow physicians and patients to personalize treatments.
A 5% weight loss in obese patients can improve their health and reduce the incidence of obesity-related complications. Thus, effective treatments and interventions are essential for obese people. The current preferred treatment for obesity is lifestyle interventions, such as controlling diet and strengthening exercises. However, these measures further trigger the body’s adaptive physiological responses, leading to increased appetite and a lower resting metabolic rate. Thus, it is difficult for obese people to achieve weight loss only through lifestyle interventions. Bariatric surgery is an effective treatment for obesity, but it is not the first choice because of its invasive nature. Conversely, pharmacotherapy is a non-invasive approach that can help people with obesity to adhere to weight-loss strategies, improve their quality of life, and reduce the risk of comorbidities.
Currently, very few weight-loss drugs have been approved for use by the FDA, other than Lorcaserin and Orlistat, which have relatively modest clinical efficacy and have not been widely used in clinical practice or well known to the public. Additionally, phentermine is not the best choice for cardiovascular disease patients because of its adverse effects even if it has a better curative effect. Thus, GLP-1RAs bring hope to obese people.
Global Perspective on GLP-1 RA Costs and Availability
Global prices vary. Prices were not found for any of these drugs in Austria or Belgium. List prices are not necessarily net prices paid as manufacturers provide insurer rebates and patient coupons. Wegovy is available in only a few European Union markets at this point, and not available in Australia and some other countries due to shortages for people using semaglutide for diabetes.
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