Tirzepatide was more cost-effective than semaglutide in patients with knee osteoarthritis and obesity, according to a modeling study.
Compared with diet and exercise, tirzepatide added nearly one quality-adjusted life-year (QALY) and had an incremental cost-effectiveness ratio (ICER) of $57,400 per QALY. In direct comparison, tirzepatide provided greater health benefits at lower costs than semaglutide.
When bariatric surgery was included, Roux-en-Y gastric bypass yielded more QALYs at lower costs than glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Sleeve gastrectomy was also cost-effective compared with nonsurgical strategies.
Researchers used the Osteoarthritis Policy Model to estimate lifetime costs and outcomes. The base-case cohort had a mean age of 56 years, mean body mass index (BMI) of 40.3 kg/m², and moderate to severe pain scores. Interventions assessed included usual care, diet and exercise, semaglutide, tirzepatide, sleeve gastrectomy, and Roux-en-Y gastric bypass.
From the health care perspective at baseline, usual care produced 9.59 QALYs at a lifetime cost of $222,300. Diet and exercise produced 9.75 QALYs at $226,300. Semaglutide produced 10.48 QALYs at $273,500, while tirzepatide produced 10.68 QALYs at $280,000. Compared with usual care, diet and exercise had an ICER of $25,400 per QALY. Compared with diet and exercise, tirzepatide had an ICER of $57,400 per QALY.
Sensitivity analyses showed tirzepatide was cost-effective in 64% of simulations and semaglutide in 34% at a willingness-to-pay threshold of $100,000 per QALY. Results were most influenced by drug costs, treatment efficacy, and baseline BMI. Lowering the cost of tirzepatide improved cost-effectiveness, while higher BMI levels favored surgical strategies.
“Our findings suggest that, when added to usual osteoarthritis care, tirzepatide use could optimize resource allocation for patients ineligible for or unwilling to pursue bariatric surgery,” said Elena Losina, PhD, Orthopaedics and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital and Harvard Medical School.
The model assumed tirzepatide reduced BMI by 23% in patients without diabetes and 15% in those with diabetes. Semaglutide reduced BMI by 15% and 10%, respectively. Both agents reduced pain substantially in the first year, with tirzepatide achieving a 58% pain decrease and semaglutide achieving a 57% pain decrease. Annual drug costs varied by diabetes status: tirzepatide cost $10,500 for patients without diabetes and $4,300 for those with diabetes, while semaglutide cost $8,600 for patients without diabetes and $4,300 for those with diabetes.
Limitations included reliance on data from multiple sources, assumptions about long-term weight and pain trajectories, and uncertainty in drug cost projections and discontinuation rates.
“The strong correlation between substantial weight loss and reduction in knee pain (and disability) warrants the inclusion of GLP-1 receptor agonists in the treatment options for patients with obesity and knee osteoarthritis,” editorial coauthor David T. Felson, MD, MPH, of Boston University, wrote.
Both semaglutide and tirzepatide were cost-effective compared with usual care, with tirzepatide providing the most favorable outcomes among GLP-1 RAs. Bariatric surgery, particularly Roux-en-Y gastric bypass, remained the most effective and cost-saving intervention.
The study was funded by the Arthritis Foundation and the National Institute of Arthritis and Musculoskeletal and Skin Diseases and was published on September 16, 2025.
Source: Annals of Internal Medicine
