The Cost-Effectiveness of Semaglutide and Tirzepatide for Patients With Knee Osteoarthritis and Obesity

Sep 15, 2025Annals of internal medicine

Cost-Effectiveness of Semaglutide and Tirzepatide in People with Knee Osteoarthritis and Obesity

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Abstract

Tirzepatide may offer greater health benefits at lower costs than semaglutide, with a cost-effectiveness ratio of $57,400 per quality-adjusted life year (QALY) compared to diet and exercise.

Both tirzepatide and semaglutide are associated with substantial weight loss and pain reduction in patients with knee osteoarthritis and obesity.
Roux-en-Y gastric bypass (RYGB) is linked to better health outcomes and lower costs compared to both GLP1RAs, with a cost-effectiveness ratio of $30,700 per QALY versus laparoscopic sleeve gastrectomy (LSG).
Tirzepatide has a 64% probability of being cost-effective at a $100,000 per QALY threshold, while semaglutide has a 34% probability.
Tirzepatide's cost-effectiveness is sensitive to changes in medication costs, treatment effectiveness, and initial body mass index (BMI) of the cohort.
Data were derived from multiple sources, which may limit the findings.

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BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP1RAs) lead to substantial weight loss and pain reduction in persons with knee osteoarthritis and obesity.

OBJECTIVE: To evaluate the cost-effectiveness of 2 GLP1RAs, semaglutide and tirzepatide, for patients with osteoarthritis and obesity.

DESIGN: Osteoarthritis Policy Model, a validated microsimulation model of knee osteoarthritis, to estimate lifetime benefits and costs of weight loss strategies.

DATA SOURCES: Published data to derive treatment-related weight loss, pain reduction, and costs of GLP1RAs from the U.S. Office of Health Policy.

TARGET POPULATION: Persons with knee osteoarthritis and obesity in the United States. The base-case cohort had a Western Ontario and McMaster Universities Osteoarthritis Index pain score of 71 (0 to 100, 100 worst) and a mean body mass index (BMI) of 40 kg/m. 2

TIME HORIZON: Lifetime.

PERSPECTIVE: Health care, societal.

INTERVENTION: Semaglutide, tirzepatide, laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), and diet and exercise.

OUTCOME MEASURES: Quality-adjusted life-years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs).

RESULTS OF BASE-CASE ANALYSIS: Tirzepatide provided greater health benefits at lower costs than semaglutide and yielded a $57 400 per QALY ICER versus diet and exercise. For those eligible, RYGB provided greater health benefits at lower costs than the 2 GLP1RAs and had a $30 700 per QALY ICER versus LSG.

RESULTS OF SENSITIVITY ANALYSIS: Tirzepatide's ICER was most sensitive to changes in medication costs, treatment efficacy, and cohort baseline BMI. Tirzepatide had a 64% and semaglutide had a 34% probability of being cost-effective at a $100 000 per QALY threshold.

LIMITATION: Data from multiple sources.

CONCLUSION: Both tirzepatide and semaglutide would be widely considered cost-effective when compared directly with usual care. Tirzepatide would offer the most favorable return on investment to decision makers whose cost-effectiveness thresholds exceed $57 400 per QALY.

PRIMARY FUNDING SOURCE: The Arthritis Foundation and National Institute of Arthritis and Musculoskeletal and Skin Diseases.