A new study published in the Annals of Internal Medicine reports that the weight-loss medications tirzepatide and semaglutide are cost-effective treatment options for individuals with knee osteoarthritis and obesity, with tirzepatide providing the greatest overall value.
Tirzepatide is a 39–amino acid synthetic polypeptide that acts as a dual agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. This combined action, sometimes referred to as a “twincretin” effect, enhances insulin release, suppresses glucagon, improves insulin sensitivity, and augments weight reduction, leading to superior metabolic and glycemic outcomes. In contrast, semaglutide is a selective GLP-1 receptor agonist, closely resembling human GLP-1, that improves glucose control by stimulating insulin secretion, lowering glucagon levels, slowing gastric emptying, and suppressing appetite. While both medications support weight loss and metabolic improvement, tirzepatide’s dual-receptor activity has been shown to achieve greater overall efficacy.
The study highlights the importance of these medications in managing knee osteoarthritis, where excess body weight contributes to pain and accelerates joint damage. Using the Osteoarthritis Policy Model, a validated microsimulation tool, researchers compared the lifetime costs and health outcomes of tirzepatide, semaglutide, laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), and lifestyle-based interventions such as diet and exercise. The analysis was conducted in a U.S. population with an average body mass index (BMI) of 40 and severe baseline pain, considering both healthcare and societal perspectives.
Results showed that tirzepatide provided greater health benefits at lower costs compared with semaglutide, with an incremental cost-effectiveness ratio (ICER) of $57,400 per quality-adjusted life-year (QALY) versus diet and exercise. For patients eligible for bariatric surgery, RYGB was the most cost-effective intervention, with an ICER of $30,700 per QALY compared to LSG. While semaglutide was cost-effective, it was less favorable than tirzepatide across both cost and outcome measures. Sensitivity analyses identified drug price, treatment efficacy, and baseline BMI as key drivers of cost-effectiveness. At a willingness-to-pay threshold of $100,000 per QALY, tirzepatide had a 64% probability of being cost-effective compared to 34% for semaglutide.
A related economic evaluation by Hwang et al. reached a similar conclusion, noting that while both medications offer substantial long-term health benefits, their current prices limit cost-effectiveness. The authors emphasized that lowering drug costs will be critical to ensuring equitable access to these therapies.
The findings suggest that both tirzepatide and semaglutide represent valuable options for managing obesity-related osteoarthritis, but tirzepatide stands out as the stronger investment for healthcare systems aiming to improve long-term outcomes. However, as the study relied on data synthesized from multiple sources, the authors caution that results may vary as more real-world evidence becomes available.
References
- Farzam K, Patel P. Tirzepatide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Sept 17]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK585056/
- Betensky DJ, Smith KC, Katz JN, Yang C, Hunter DJ, Collins JE, Feldman CH, Messier SP, Kim JS, Selzer F, Paltiel AD, Losina E. The Cost-Effectiveness of Semaglutide and Tirzepatide for Patients With Knee Osteoarthritis and Obesity. Ann Intern Med. 2025 Sep 16.
- Kommu S, Whitfield P. Semaglutide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Sept 17]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK603723/
- Hwang JH, Laiteerapong N, Huang ES, Kim DD. Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults. JAMA Health Forum. 2025 Mar 7;6(3):e245586.