Tirzepatide vs semaglutide and liraglutide for weight loss in patients with overweight or obesity without diabetes: A short-term cost-effectiveness analysis in the United States

Abstract

BACKGROUND:

Glucagon-like peptide-1 receptor agonists and their analogues have emerged as effective pharmacotherapies for obesity.

OBJECTIVE:

To assess the short-term cost-effectiveness of subcutaneous tirzepatide, semaglutide, liraglutide, and oral semaglutide for managing obesity or overweight in patients without diabetes.

METHODS:

A decision tree model was developed using a 68-week time window with consideration of serious adverse events and treatment discontinuation from a US payer’s perspective. The study population were adults with obesity or overweight with at least 1 weight-related comorbidity but without diabetes. Clinical data were obtained from clinical trials. Model utilities, disutilities, and the costs of serious adverse events were sourced from published literature. Medication costs were assigned from Red Book. All costs were calculated in 2024 US dollars. The incremental cost-effectiveness ratio was calculated based on the cost per quality-adjusted life-year (QALY) gained. A willingness-to-pay threshold of $150,000 per QALY was used. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the effect of parameter uncertainty on the results.

RESULTS:

In the base-case analysis, both subcutaneous tirzepatide and oral semaglutide were cost-effective vs subcutaneous liraglutide and subcutaneous semaglutide. Compared with oral semaglutide, subcutaneous tirzepatide was cost-effective, with an incremental cost-effectiveness ratio of $34,212 per QALY gained. Sensitivity analyses indicated the results were highly sensitive to medication costs and the effectiveness of medications. The probabilistic sensitivity analysis suggested that subcutaneous tirzepatide was most likely to remain cost-effective, with a 98% probability at a willingness to pay of $150,000 per QALY compared with other medications.

CONCLUSIONS:

Subcutaneous tirzepatide and oral semaglutide were cost-effective therapies compared with subcutaneous liraglutide and subcutaneous semaglutide for the short-term management of obesity in adults without diabetes. At or under a willingness-to-pay threshold of $150,000 per QALY, subcutaneous tirzepatide was most cost-effective, surpassing oral semaglutide. These findings provide valuable insights for health care decision-makers in selecting antiobesity medications.

Plain language summary

We compared the cost-effectiveness of tirzepatide, semaglutide (injectable and oral), and liraglutide over a 68-week period in adults with obesity or overweight but without diabetes. Overall, tirzepatide was the most cost-effective option. Compared with oral semaglutide, tirzepatide had an incremental cost of $34,212 for each quality-adjusted life-year (QALY) gained. Oral semaglutide was cost-effective compared with injectable semaglutide and liraglutide. Tirzepatide may be preferred for obesity among glucagon-like peptide-1 receptor agonists and their analogues.

Implications for managed care pharmacy

This study evaluated the cost-effectiveness of subcutaneous tirzepatide, oral semaglutide, subcutaneous semaglutide, and subcutaneous liraglutide for obesity management in adults without diabetes. Tirzepatide was the most cost-effective, with an incremental cost-effectiveness ratio of $34,212 per QALY gained. Oral semaglutide was cost-effective compared with injectable semaglutide and liraglutide. These findings provide important implications for managed care decision-making, particularly in formulary design, coverage policies, and cost-containment strategies, helping payers optimize coverage for effective obesity treatments.

The public health burden of obesity has increased worldwide. ¹ In the United States, the prevalence of obesity has surged to nearly 42% in a recent report. ² Obesity is strongly associated with a wide range of health conditions, including diabetes, kidney disease, osteoarthritis, sleep apnea, fatty liver disease, cardiovascular disease, and certain types of cancer. ^{3 , 4} The estimated annual medical cost associated with obesity was nearly $173 billion in 2019. ⁵ Furthermore, adults with obesity incurred higher medical costs than individuals with healthy weight. ⁶ Given this significant economic impact, evaluating the cost-effectiveness of obesity treatments is in great need for optimizing health care resource allocation and improving patient outcomes.

Antiobesity medications are recommended in conjunction with lifestyle modifications to manage obesity. The US Food and Drug Administration (FDA) has approved 6 medications for long-term use, including orlistat, phentermine plus topiramate, naltrexone plus bupropion, subcutaneous liraglutide, subcutaneous semaglutide, and subcutaneous tirzepatide. ⁷ The use of gut-hormone receptor agonists represents a new therapeutic option for obesity. ⁸ Semaglutide and liraglutide are glucagon-like peptide-1 receptor agonists (GLP-1 RAs) ⁹ ; tirzepatide is a dual GLP-1 receptor agonist and glucose-dependent insulinotropic polypeptide. ¹⁰ These GLP-1 RAs and analogues have become popular and have been increasingly used compared with traditional antiobesity medications. ¹¹

Before the approval of tirzepatide for obesity, subcutaneous semaglutide appeared to be the most cost-effective option among various injectable medications. A previous cost-effectiveness analysis found that subcutaneous semaglutide was a cost-effective alternative to subcutaneous liraglutide, dulaglutide, and exenatide injections for the treatment of obesity. ¹² In November 2023, subcutaneous tirzepatide was approved for chronic weight management in adults with obesity or overweight accompanied by at least 1 weight-related condition. ¹³ Evidence showed that tirzepatide was likely to be cost-effective compared with semaglutide for the treatment of type 2 diabetes in both short-term and long-term cost-effectiveness analyses. ^{14 – 16} With the emergence of new evidence from the latest published clinical trials (SURMOUNT-3) in patients with obesity, ¹⁷ there was a compelling need to assess the cost-effectiveness of tirzepatide, incorporating all available data. However, no prior studies have evaluated its economic value for obesity treatment in nondiabetic populations after the approval of tirzepatide.

Moreover, oral semaglutide has also shown promising results in patients with obesity, as demonstrated by the OASIS-1 trial, ¹⁸ yet no previous study has explored the cost-effectiveness of oral semaglutide as an antiobesity treatment. Given the increasing demand for convenient, noninjectable treatment options, it is important to assess the economic and clinical value of oral medication vs injectable GLP-1 RA therapies in obesity management.

A key reason for evaluating tirzepatide, semaglutide, and liraglutide in nondiabetic populations is the different mechanism and treatment goals between patients with and without diabetes. For treating diabetes, they primarily work by enhancing insulin secretion, reducing glucagon levels, and improving glucose homeostasis, whereas in obesity treatment, they function by modulating appetite, decreasing food intake, and promoting long-term weight loss. For patients with diabetes, they are primarily prescribed for glycemic control. However, in patients without diabetes, the primary treatment objective is weight management. These differences in dosing, expected outcomes, and treatment duration requires a separate cost-effectiveness evaluation for patients without diabetes.

This study was designed to assess the short-term cost-effectiveness of subcutaneous tirzepatide, semaglutide, liraglutide and oral semaglutide for managing obesity or overweight in patients without diabetes in the United States. The Ohio State University Research Ethics Committee has confirmed that no ethical approval is required.

Methods

MODEL OVERVIEW

We developed a decision tree model using TreeAge Pro 2024 to determine the cost-effectiveness of subcutaneous liraglutide, subcutaneous semaglutide, oral semaglutide (50 mg), and subcutaneous tirzepatide in patients with obesity or overweight and without diabetes over a 68-week time window to reflect the duration of the clinical trials used as data sources. The model considered serious adverse events (SAEs), treatment discontinuation, and costs related for treatment of SAEs from a US payer’s perspective. The model included 4 treatment arms (Figure 1): subcutaneous tirzepatide, oral semaglutide, subcutaneous semaglutide, and subcutaneous liraglutide. The decision tree model was used to estimate the cost and utility for each arm. Modeled events included SAEs and treatment discontinuation. An SAE is any undesirable medical occurrence associated with a medical outcome that results in death, life-threatening conditions, hospitalization, permanent disability, birth defects, the need for medical intervention to prevent lasting harm, or other serious medical complications requiring urgent care. ¹⁹

FIGURE 1.

Decision Tree Model for the Short-Term Cost-Effectiveness of Tirzepatide Injection vs Semaglutide Tablet vs Semaglutide Injection vs Liraglutide Injection

SAE = serious adverse event.

The study was conducted and reported in accordance with the Consolidated Health Economic Evaluation Reporting Standard recommendations, ensuring transparency and quality in the economic evaluation. ²⁰

STUDY POPULATION

The study population comprised adults aged 18 years or older with a body mass index (BMI) of greater than or equal to 30 kg/m² or greater than or equal to 27 kg/m² with at least 1 weight-related comorbidity. Patients with type 1 or type 2 diabetes were excluded.

MODEL INPUTS

Clinical data on BMI reduction (kg/m²) at the end of treatment, probability of discontinuation of treatment, and probability of SAEs were obtained from the following randomized controlled trials: data for liraglutide from STEP 8 ²¹ and SCALE ²² ; data for subcutaneous semaglutide from STEP 1, ²³ STEP 3, ²⁴ , STEP 4, ²⁵ , and STEP 8 ²¹ ; data for oral semaglutide from OASIS 1 ¹⁸ ; and data for tirzepatide from SURMOUNT-1 ²⁶ and SURMOUNT-3. ¹⁷ The patient baseline characteristics are generally similar among the trials and are summarized in Supplementary Table 1 ^{(339.9KB, pdf)} (available in online article).

The model utilities, disutilities, and costs are summarized in Table 1. The baseline utility value for obesity was set at 0.80 quality-adjusted life-years (QALYs). ²⁷ Each BMI unit decrease was associated with a 0.01845 increase in QALYs. ²⁸ The weight loss effects of treatments were most pronounced within the initial 20 weeks, with most patients experiencing 55% to 90% of the total anticipated weight loss. SAEs led to a utility decrease of 0.04 QALYs. ²⁹ Model costs included the cost of the medication and the cost of treatment for SAEs. Costs of subcutaneous liraglutide, subcutaneous semaglutide, oral semaglutide, and subcutaneous tirzepatide were obtained as wholesale acquisition cost from Red Book. ³⁰ Subcutaneous liraglutide is available in multidose pens, sold in packs of 2 or 3 pens per box, with each pen containing 18 mg of liraglutide. Given the recommended dose of 3 mg per day, a single pack lasts 12 to 18 days, requiring 2 to 3 packs per month. Subcutaneous semaglutide and subcutaneous tirzepatide are supplied in single-dose pens, typically packaged with 4 pens per pack. They are given weekly, providing a 1-month supply. The cost remains consistent across different strengths for these medications. Oral semaglutide is provided in 30-tablet bottles (1-month supply), and pricing for this strength (50 mg) remains uncertain as it is not yet FDA approved for obesity. We used the cost for semaglutide in another strength and assumed the cost for a different strength to be the same. The monthly cost for each medication is summarized in Table 1. The cost of SAEs was determined from previous published literature. ³¹ All costs were calculated in 2024 US dollars, with historical costs adjusted for inflation using the Consumer Price Index to maintain consistency and accuracy in the economic evaluations. ³²

TABLE 1.

Model Input

Parameter	Base-case value	Lower limit	Upper limit	Data source	PSA distribution
Probability
Probability of SAE (tirzepatide)	0.06	0.045	0.075	SURMOUNT-1 26 and SURMOUNT-3 17	β
Probability of SAE (liraglutide)	0.11	0.0825	0.1375	STEP 8 21 and SCALE 22	β
Probability of SAE (semaglutide tablet)	0.1	0.075	0.125	OASIS 1 18	β
Probability of SAE (semaglutide injection)	0.09	0.0675	0.1125	STEP 1, 23 STEP 3, 24 STEP 4, 25 and STEP 8 21	β
Probability of DC (tirzepatide)	0.17	0.1275	0.2125	SURMOUNT-1 26 and SURMOUNT-3 17	β
Probability of DC (liraglutide)	0.28	0.21	0.35	STEP 8 21 and SCALE 22	β
Probability of DC (semaglutide tablet)	0.14	0.105	0.175	OASIS 1 18	β
Probability of DC (semaglutide injection)	0.14	0.105	0.175	STEP 1, 23 STEP 3, 24 STEP 4, 25 and STEP 8 21	β
Cost, $
Monthly cost (tirzepatide)	1,059	742	1,059	Red Book 30	γ
Monthly cost (semaglutide injection)	1,349	944	1,349	Red Book 30	γ
Monthly cost (liraglutide)	1,362	953	1,362	Red Book 30	γ
Monthly cost (semaglutide tablet)	968	677	1,259	Red Book 30	γ
Cost of SAE	16,265	11,385	21,144	Hug et al 31	γ
Clinical data
Total BMI reduction (liraglutide)	3	2.25	3.75	STEP 8 21 and SCALE 22	Normal
Total BMI reduction (semaglutide injection)	5.6	4.2	7	STEP 1, 23 STEP 3, 24 STEP 4, 25 and STEP 8 21	Normal
Total BMI reduction (semaglutide tablet)	5.6	4.2	7	OASIS 1 18	Normal
Total BMI reduction (tirzepatide)	8.2	6.15	10.25	SURMOUNT-1 26 and SURMOUNT-3 17	Normal
BMI reduction at week 20 (liraglutide)	2.7	2.025	3.375	STEP 8 21 and SCALE 22	Normal
BMI reduction at week 20 (semaglutide injection)	3.3	2.475	4.125	STEP 1, 23 STEP 3, 24 STEP 4, 25 and STEP 8 21	Normal
BMI reduction at week 20 (semaglutide tablet)	3.5	2.625	4.375	OASIS 1 18	Normal
BMI reduction at week 20 (tirzepatide)	4.5	3.375	5.625	SURMOUNT-1 26 and SURMOUNT-3 17	Normal
Discontinuation time, weeks	20	15	25	Assumption	Normal
Weekly BMI increase after DC	0.083	0.06225	0.10375	Aronne et al 33	Normal
Utility
QALY for initial state	0.8	0.6	0.88	Rothberg et al 27	β
Reduced QALY of SAE	0.04	0.03	0.05	Shingler et al 29	β
Increased QALY per BMI reduction	0.01845	0.0138	0.023	Dennett et al 28	β
Reduced QALY per BMI increase	0.003	0.00225	0.00375	Kortt et al 34	β

BMI = body mass index; DC = discontinuation; PSA = probabilistic sensitivity analysis; QALY = quality-adjusted life-year; SAE = serious adverse event.

ASSUMPTIONS

In the economic model, we made several assumptions. First, the therapy discontinuation for all medications occurred at the end of week 20, consistent with the observation that most of the adverse drug events associated with discontinuation have occurred within this timeframe. Second, whereas the tirzepatide trial lasted 72 weeks, those for the other medications lasted for 68 weeks. To ensure a consistent 68-week comparison window, we assumed that the BMI reduction for tirzepatide did not change significantly from week 68 to week 72 based on the data provided in the clinical trials. ^{17 , 26} Additionally, the model presupposed that the cost of oral semaglutide 50 mg was equivalent to other strengths, as official pricing for this formulation is not yet available. For patients discontinuing treatment, the model incorporated a consistent BMI regain rate. Specifically, data from tirzepatide discontinuation indicated a BMI rebound of 4.3 units between weeks 36 and 88, translating to 0.083 kg/m²/week, ³³ which was extrapolated to estimate weight regain after treatment. Lastly, the model assumed that for each unit increase in BMI, the quality of life decreased by 0.003, ³⁴ reflecting the negative impact of weight regain on patient-reported outcomes.

ASSESSMENT OF COST-EFFECTIVENESS

The medication effectiveness of BMI reduction was measured in QALYs. The outcome measure was the incremental cost-effectiveness ratio (ICER), calculated as the ratio of cost differences to QALY differences between different treatments. The willingness-to-pay (WTP) threshold of $150,000 per QALY was used to evaluate the cost-effectiveness of interventions, consistent with current literature, which supports $100,000 or $150,000 per QALY as appropriate thresholds for cost-effectiveness analyses for obesity and diabetes treatments. ³⁵

SENSITIVITY ANALYSES

To evaluate the impact of parameter uncertainty on cost-effectiveness results, sensitivity analysis was conducted using a Tornado diagram for one-way sensitivity analysis and a probabilistic sensitivity analysis (PSA) to assess a wide range of parameter combinations. Costs for subcutaneous liraglutide, subcutaneous semaglutide, and subcutaneous tirzepatide varied by −30% of their base-case values to reflect discounts typically applied by wholesalers in the drug supply chain. ^{36 , 37} The cost of oral semaglutide was adjusted by ±30% of the base-case values given the unknown price of the new dosage of the drug. The cost of SAEs was also adjusted by ±30% of their base-case values. The change in BMI and utility parameters were varied by ±25% of their base-case value.

To conduct the PSA, we used a simultaneous sampling approach for all distribution parameters. Costs were modeled with a γ distribution, utilities with a β distribution, and BMI reduction with a normal distribution. We introduced variability of BMI reduction at 25% of the mean value, in line with previous literature. ³⁵ The base-case values served as the mean for these distributions. The analysis ran 10,000 Monte Carlo simulations per treatment group, and cost-effectiveness was gauged by the proportion of simulations in which a treatment’s value fell below the WTP threshold for each medication.

Results

BASE-CASE RESULTS

In the base-case analysis, subcutaneous tirzepatide and oral semaglutide emerged as cost-effective vs subcutaneous liraglutide and subcutaneous semaglutide. Compared with oral semaglutide, subcutaneous tirzepatide is cost-effective, with an ICER of $34,212 per QALY gained at 68 weeks. Based on a WTP threshold of $150,000 per QALY, subcutaneous tirzepatide was most cost-effective among the 4 medications (Table 2).

TABLE 2.

Base-Case Results

Strategy	Cost, $	Incremental cost, $	QALYs	Incremental QALYs	ICER, $/QALY gained
Semaglutide tablet	18,489	—	1.1107	—	—
Tirzepatide injection	19,537	1,047	1.1413	0.0306	34,212
Semaglutide injection	24,963	5,427	1.1104	−0.0309	Dominated
Liraglutide injection	26,087	6,551	1.0828	−0.0585	Dominated

All dollars are in 2024 $.

ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year.

SENSITIVITY RESULTS

Figure 2 highlights the most influential sensitivity analyses for comparing subcutaneous tirzepatide with oral semaglutide over a 68-week period. The model was most sensitive to the cost of oral semaglutide, the cost of subcutaneous tirzepatide, and the BMI reduction effect of subcutaneous tirzepatide and oral semaglutide. When the cost of oral semaglutide is below $764, tirzepatide will no longer be cost-effective at a WTP threshold of $150,000 per QALY. Notably, even with variations in base-case values for the remaining variables, the ICER for subcutaneous tirzepatide vs oral semaglutide remained below the $150,000 per QALY threshold.

FIGURE 2.

Tornado Diagram of One-Way Sensitivity Analysis for Tirzepatide Injection vs Semaglutide Tablet for 68 Weeks

Model parameters were varied between the lower and upper limits of ranges. The length of the bar indicates the ICER associated with the range.

BMI = body mass index; ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year; SAE = serious adverse event; WTP = willingness to pay.

Oral semaglutide remained cost-effective vs subcutaneous liraglutide for all one-way sensitivity analyses (Supplementary Figure 1 ^{(339.9KB, pdf)} ). Oral semaglutide was also more cost-effective than subcutaneous semaglutide for all one-way sensitivity analyses, except when the cost of subcutaneous semaglutide was less than $975, although oral semaglutide remained cost-effective (Supplementary Figure 2 ^{(339.9KB, pdf)} ).

The PSA and the cost-effectiveness acceptability curves suggested that subcutaneous tirzepatide had a larger potential of being cost-effective when compared with oral semaglutide, with a 97.8% probability at a WTP of $150,000 per QALY at 68 weeks. At a more conservative WTP threshold of $100,000 per QALY, subcutaneous tirzepatide had a 98.4% probability of being cost-effective at 68 weeks vs oral semaglutide (Figure 3).

FIGURE 3.

CE Acceptability Curves From Probability Sensitivity Analyses Results for 68 Weeks

CE = cost-effectiveness; QALY = quality-adjusted life-year.

Discussion

This study is the first cost-effectiveness analysis comparing subcutaneous tirzepatide, oral semaglutide, subcutaneous semaglutide, and subcutaneous liraglutide using a decision tree model. This analysis is also the first to include data from recently published clinical trials of tirzepatide following its approval for the treatment of obesity. The results demonstrated that subcutaneous tirzepatide was the most cost-effective option for adults with obesity without diabetes, being cost-effective at a WTP threshold of $150,000 per QALY gained compared with oral semaglutide and dominating over both subcutaneous liraglutide and subcutaneous semaglutide over a 68-week time window.

The sensitivity analysis highlighted key cost-effectiveness drivers, such as medication costs and the BMI reduction effects of subcutaneous tirzepatide and oral semaglutide on the ICER. Given the dynamic pricing of new obesity therapies and the potential for insurance coverage variations, these factors should be monitored closely by payers and policymakers when making reimbursement decisions. Furthermore, PSAs confirmed that subcutaneous tirzepatide remained cost-effective compared with oral semaglutide.

With a sharply rising prevalence of obesity, there is a growing focus on developing medications based on enteropancreatic hormones. ³⁸ Subcutaneous semaglutide has been shown to be cost-effective among GLP-1 RAs. ¹² Tirzepatide, as a newer medication for the chronic management of obesity, could rapidly achieve and sustain weight loss effect in adults with obesity. ³⁹ In the SURMOUNT-1 and SURMOUNT-3 trials, the weight loss ranged between 15% and nearly 21% after 72 weeks of treatment. ^{17 , 26} This represented clinically significant greater and sustained weight loss than approved GLP-1 RAs. ^{40 , 41} This efficacy outcome makes tirzepatide a favorable medication compared with other medications for obesity.

In the real-world settings, however, selection of antiobesity medications is not solely based on efficacy but also depends on other factors such as previous attempts to lose weight, comorbid medical conditions, coadministration of other medications, adverse effects from medications, insurance coverage, and patient preferences. ^{42 , 43} Despite its favorable cost-effectiveness profile, tirzepatide may not be the best option for all patients. Many patients prefer oral medications over injectables; therefore, oral semaglutide might be an alternative for those who would prefer oral regimens. Moreover, tirzepatide is not recommended for patients with a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. ⁴⁴ Although cost-effectiveness analyses favor tirzepatide, actual patient access depends on formulary placement, insurance coverage, and copay structures. Many insurers may impose step therapy requirements, favoring other GLP-1 RAs before approving tirzepatide. Lastly, adverse events and discontinuation rates should be considered in real-world settings. Given these practical constraints, clinicians, formulary decision-makers, and payers should use a patient-centered approach, balancing efficacy, costs, patient preferences, and safety considerations when selecting obesity pharmacotherapy.

Strengths of our study include a comprehensive comparison of the cost-effectiveness of the most effective antiobesity medications as well as considerations of costs related to treatment discontinuation and SAEs in our analysis. We used the dollars per QALY gained to evaluate the economic value of the treatment, which provided a more holistic view of its impact on both health outcomes and costs.

LIMITATIONS

However, this study has several limitations. First, it examined short-term weight loss effects, with long-term efficacy remaining uncertain. Given the chronic nature of obesity, future research should conduct a long-term cost-effectiveness analysis of tirzepatide to better assess its role in the long-term management of obesity. Second, the efficacy outcomes were derived from separate clinical trials, rather than a direct head-to-head comparison of multiple antiobesity agents. This introduces potential variability in patient populations and study designs, suggesting a need for future trials directly comparing these treatments. Third, the model did not capture potential cardiovascular benefits of these medications. Although GLP-1 RAs have demonstrated cardiovascular risk reduction in patients with diabetes, these effects were not reported in these obesity trials yet. Future research should consider incorporating cardiovascular outcome data into the analysis, as improvements in cardiovascular health may significantly impact overall cost-effectiveness and health care costs. Fourth, given that semaglutide 50-mg tablet is not approved for chronic obesity management, the cost of oral semaglutide was assumed to be equivalent to lower-dose formulations used for diabetes treatment If pricing for oral semaglutide 50 mg differs significantly from our assumption, it may impact the results of our cost-effectiveness analysis. This analysis used wholesale acquisition costs, which may not represent actual health care payer costs, although an attempt to reflect the real-world cost was made in our sensitivity analysis described under the Methods section. We assumed fixed BMI regain rates based on data from the SURMOUNT trial. Although this ensured comparability across treatments, real-world regain rates may vary owing to various factors. To address this, we conducted sensitivity analyses to assess its impact on cost-effectiveness. Future research should use long-term real-world data on weight maintenance after discontinuation and refine these estimates to improve the generalizability of research findings. Lastly, the trial included adults aged 18 years or older with a BMI of greater than or equal to 30 kg/m² or greater than or equal to 27 kg/m² with at least 1 weight-related comorbidity, but patients with type 1 or type 2 diabetes were excluded. This exclusion limits the generalizability of our findings, as many patients with obesity also have diabetes or other chronic conditions that may impact treatment response in real-world settings. Addi­tionally, clinical trials typically report higher medication adherence rates than real-world settings. Future cost-effectiveness studies using real-world data and long-term treatment effects are needed to validate our findings across diverse patient populations.

Conclusions

Subcutaneous tirzepatide and oral semaglutide may be cost-effective interventions in the first 68 weeks of treatment, having dominance over subcutaneous semaglutide and sub­cu­taneous liraglutide in adults with obesity or overweight. At or under a WTP threshold of $150,000 per QALY, subcutaneous tirzepatide was found to be the most cost-effective, surpassing oral semaglutide as an antiobesity medication. Future studies should focus on long-term cost-effectiveness evaluations by incorporating real-world medication adherence, weight maintenance after treatment discontinuation, and long-term health benefits such as cardiovascular outcomes.