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. 2025 Nov;178(11):1549-1560.
doi: 10.7326/ANNALS-24-03609. Epub 2025 Sep 16.

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

Affiliations

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

Daniel J Betensky et al. Ann Intern Med. 2025 Nov.

Abstract

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/m2.

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.

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Conflict of interest statement

Disclosures: Disclosure forms are available with the article online.