Tirzepatide more cost-effective than semaglutide in some patients with knee osteoarthritis, study finds

Semaglutide and tirzepatide were cost-effective compared with usual care for knee osteoarthritis, with tirzepatide offering a more favorable return on investment, a recent cost analysis found.

Researchers used the Osteoarthritis Policy Model to compare the cost-effectiveness of the two glucagon-like peptide-1 (GLP-1) receptor agonists in patients with osteoarthritis and obesity undergoing six treatment plans: usual care, usual care plus diet and exercise, usual care plus semaglutide, usual care plus tirzepatide, usual care plus laparoscopic sleeve gastrectomy, and usual care plus Roux-en-Y gastric bypass (RYGB). Primary outcomes were lifetime quality-adjusted life-years (QALYs), medical costs in 2024 U.S. dollars, and incremental cost-effectiveness ratios (ICERs). The results were published Sept. 16 by Annals of Internal Medicine.

In the primary analysis excluding surgical strategies, usual care led to 9.59 QALYs compared with 9.75 for usual care plus diet and exercise, 10.48 for usual care plus semaglutide, and 10.68 for usual care plus tirzepatide. Adding diet and exercise to usual care resulted in an ICER of $25,400 per QALY, while adding tirzepatide led to an ICER of $57,400 per QALY. There was greater clinical benefit at lower costs with tirzepatide when analyzed incrementally compared to semaglutide.

In the secondary analysis, in which all patients were considered eligible for bariatric surgery, the researchers found that for patients with a BMI above 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 high annual recurring costs required for GLP-1 receptor agonists.

The authors wrote that nearly 30 million people in the U.S. have knee osteoarthritis and many are overweight or obese. “Clinicians may consider discussing the differences between these weight loss interventions, their potential benefits and harms, and currently available knee osteoarthritis care options with their eligible patients,” they wrote.

An editorial stated that dietary interventions remain a first-line treatment for obesity and painful knee osteoarthritis, as some patients achieve meaningful relief despite modest effects.

“However, on the basis of evidence from bariatric surgery studies and recent findings on semaglutide, 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,” the editorialists wrote. “Together, these strategies offer a spectrum of treatments that can be tailored to patient preferences, tolerability, and disease severity.”