Tirzepatide offers better value than semaglutide for treating knee osteoarthritis in people with obesity, costing $57,400 per quality-adjusted life-year gained compared to diet and exercise alone.
$57,400/QALYTirzepatide's cost per quality-adjusted life-year gained versus diet and exercise — well within standard cost-effectiveness thresholds
What the researchers found
Tirzepatide provided greater health benefits at lower costs than semaglutide for patients with knee osteoarthritis and obesity, with an incremental cost-effectiveness ratio (ICER) of $57,400 per quality-adjusted life-year (QALY) versus diet and exercise. At a $100,000 per QALY willingness-to-pay threshold, tirzepatide had a 64% probability of being cost-effective compared to 34% for semaglutide.
For patients eligible for bariatric surgery, Roux-en-Y gastric bypass (RYGB) provided even greater health benefits at lower costs than both GLP-1 drugs, with an ICER of $30,700 per QALY versus laparoscopic sleeve gastrectomy.
Why it matters
Millions of people live with both knee osteoarthritis and obesity, conditions that worsen each other. GLP-1 receptor agonists like semaglutide and tirzepatide have shown they can reduce both weight and knee pain, but these drugs are expensive. This study provides decision-makers with concrete data showing that both drugs represent a reasonable investment in health outcomes, with tirzepatide offering the better value — important information as payers and health systems decide whether to cover these medications for osteoarthritis patients.
The numbers in context
Tirzepatide ICER: $57,400/QALY · Semaglutide ICER: higher than tirzepatide · RYGB ICER: $30,700/QALY vs LSG · Baseline BMI: 40 kg/m² · Pain score: 71/100 · Tirzepatide cost-effective probability: 64% · Semaglutide: 34%
How the study worked
The researchers used the Osteoarthritis Policy Model, a validated microsimulation model of knee osteoarthritis, to estimate lifetime health benefits and costs. They compared five weight loss strategies: semaglutide, tirzepatide, laparoscopic sleeve gastrectomy, Roux-en-Y gastric bypass, and diet and exercise. Input data came from published clinical trials and the U.S. Office of Health Policy. The base-case cohort had a mean BMI of 40 kg/m² and a pain score of 71 out of 100. Outcomes were measured in quality-adjusted life-years and costs from healthcare and societal perspectives.
Who was studied
U.S. adults with knee osteoarthritis and obesity (mean BMI 40 kg/m²)
What this study cannot tell us
This is a modeling study based on published data rather than a head-to-head clinical trial. The results are sensitive to assumptions about medication costs, treatment efficacy, and baseline BMI. Real-world adherence, side effects, and long-term outcomes may differ from model inputs. Data were drawn from multiple sources, which may introduce heterogeneity.
How to read the evidence
This is a validated microsimulation modeling study using published clinical trial data. While it provides rigorous health economic analysis, it is not a direct clinical trial and relies on assumptions that may not fully reflect real-world outcomes. The evidence is moderate strength for informing cost-effectiveness decisions.
When this study was published
Published in 2025, this study reflects current drug pricing and clinical trial data for semaglutide and tirzepatide, making it highly relevant to ongoing coverage and reimbursement decisions.
The bigger picture
GLP-1 receptor agonists have become blockbuster drugs for weight loss and diabetes, but their high costs have sparked debate about who should get access to them. This study extends that conversation into osteoarthritis — a condition where obesity directly worsens joint damage and pain. As insurance coverage decisions for these drugs evolve, health economic analyses like this one provide evidence that payers can use to justify or restrict coverage for specific patient populations. The finding that bariatric surgery still outperforms drugs on cost-effectiveness also highlights the ongoing tension between surgical and pharmacological approaches to obesity.
Questions still open
- Would head-to-head clinical trials of tirzepatide vs. semaglutide in osteoarthritis patients confirm the modeling results?
- How would lower negotiated drug prices change the cost-effectiveness calculations?
- What is the long-term joint preservation benefit of GLP-1-mediated weight loss in osteoarthritis — does it delay or prevent knee replacement surgery?
Common questions
What does 'cost per QALY' mean and why does it matter?
Why does tirzepatide come out ahead of semaglutide in this analysis?
Read the original research
The Cost-Effectiveness of Semaglutide and Tirzepatide for Patients With Knee Osteoarthritis and Obesity.
Annals of internal medicine, 178(11), 1549-1560
Citation
Betensky, Daniel J; Smith, Karen C; Katz, Jeffrey N; Yang, Catherine; Hunter, David J; Collins, Jamie E; Feldman, Candace H; Messier, Stephen P; Kim, Jason S; Selzer, Faith; Paltiel, A David; Losina, Elena. (2025). The Cost-Effectiveness of Semaglutide and Tirzepatide for Patients With Knee Osteoarthritis and Obesity.. Annals of internal medicine, 178(11), 1549-1560. https://doi.org/10.7326/ANNALS-24-03609