A microsimulation model was used to evaluate the cost-effectiveness of two glucagon-like peptide-1 receptor agonists (GLP1RAs), semaglutide and tirzepatide, for patients with osteoarthritis and obesity compared with usual care, diet and exercise, and weight loss surgeries.

The study found that both semaglutide and tirzepatide would be cost-effective compared with usual care, with tirzepatide offering a more favorable return on investment. The results suggest tirzepatide would be more economical than semaglutide at current net prices. The study is published in Annals of Internal Medicine.

Researchers from the Orthopedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital assessed the cost-effectiveness of GLP1RAs and other weight loss interventions in patients with knee osteoarthritis and obesity using the Osteoarthritis Policy (OAPol) Model, a validated and widely published Monte Carlo microsimulation of knee osteoarthritis.

Model parameters were derived from the STEP (Semaglutide Treatment Effect in People with Obesity)-9 study. Primary outcomes were lifetime quality-adjusted life-years (QALYs), medical costs in 2024 U.S. dollars, and incremental cost-effectiveness ratios (ICERs).

They examined six clinical strategies: usual care (UC), UC plus diet and exercise, UC plus semaglutide, UC plus tirzepatide, UC plus laparoscopic sleeve gastrectomy (LSG), and UC plus Roux-en-Y gastric bypass (RYGB).

For everyone on a weight loss regimen, the model assigned a BMI and pain reduction level along with a probability of adverse events based on published clinical trial data or secondary analyses of data from randomized clinical trials.

The researchers derived weight loss associated with semaglutide from the STEP-5 and STEP-2 trials and weight loss for tirzepatide from the SURMOUNT-4 (A Study of Tirzepatide in Participants With Obesity or Overweight for the Maintenance of Weight Loss) and SURMOUNT-2 (A Study of Tirzepatide in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight) trials.

In the primary analysis excluding surgical strategies, the researchers found that UC led to 9.59 QALYs compared with 9.75 for diet and exercise, 10.48 for semaglutide, and 10.68 for tirzepatide.

Adding diet and exercise to UC resulted in an ICER of $25,400 per QALY, whereas adding tirzepatide produced an ICER of $57,400 per QALY. Tirzepatide provided greater clinical benefit at lower costs when analyzed incrementally compared to semaglutide.

In the secondary analysis, the researchers found that for persons with BMI>35 kg/m², RYGB would offer the best return on investment for cost-effectiveness thresholds above $30,700 per QALY, which may stem from the long-term weight maintenance seen after weight loss surgery compared to GLP1RA medications.

These findings should inform discussions between clinicians and patients on the differences between these weight loss interventions, their potential benefits and harms, and currently available knee osteoarthritis care options for persons with BMI>30 kg/m² and symptomatic knee osteoarthritis.