Semaglutide and tirzepatide may be cost-effective for knee osteoarthritis in patients with obesity

1. In this microsimulation model, the two glucagon-like peptide-1 receptor agonists were shown to be cost-effective when added to usual care for treating knee osteoarthritis in people with obesity.

2. Tirzepatide offered more clinical benefits at lower costs compared with semaglutide, although its effect was more dependent on factors including body mass index and cardiovascular effects.

Evidence Rating Level: 2 (Good)

Study Rundown: Obesity increases the risk for knee osteoarthritis, and people with obesity tend to present with more severe pain and functional limitations than those without obesity. Semaglutide has been associated with decreased knee pain in osteoarthritis, but use of glucagon-like peptide-1 receptor agonists (GLP1RAs) can be costly. Using a microsimulation model of knee osteoarthritis, this study aimed to assess the conditions under which management of osteoarthritis-associated knee pain and obesity using semaglutide and tirzepatide may be cost-effective. Both semaglutide and tirzepatide led to more quality-adjusted life years (QALY) and were cost-effective compared with usual care (UC). Tirzepatide generally showed greater clinical benefits at lower costs compared with semaglutide. Diet and exercise led to greater gains in QALYs compared with usual care but fewer QALYs compared with semaglutide and tirzepatide. Sensitivity analyses showed that tirzepatide became less cost-effective than semaglutide at smaller magnitudes of body mass index (BMI) reduction, when using Federal Supply Schedule costs, and when excluding its effects on major adverse cardiovascular events. The generalizability of this study is limited by the use of data from multiple sources as well as a lack of data on long-term GLP1RA weight loss efficacy or adverse events. Nevertheless, this study suggests that both tirzepatide and semaglutide may be reasonable treatments for knee osteoarthritis in people with obesity.

Click to read this study in AIM

Relevant Reading: Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis

In-Depth [prospective cohort]: This microsimulation study aimed to assess the conditions under which semaglutide and tirzepatide may be cost-effective in managing knee osteoarthritis and obesity. The study included 6 clinical strategies: UC, UC plus diet and exercise, UC plus semaglutide, UC plus tirzepatide, UC versus laparoscopic sleeve gastrectomy, and UC plus Roux-en-Y gastric bypass. Weight loss interventions were compared against adjacent strategies ranked by increasing costs and against a single common control (UC or diet and exercise). Participants were derived from the STEP (Semaglutide Treatment Effect in People with Obesity)-9 study. The resulting cohort was 81.6% women and 88.9% White non-Hispanic, with a mean age of 56 years and a mean BMI of 40.3 kg/m². In a primary analysis focused on nonsurgical options, UC led to 9.59 QALYs while diet and exercise led to 9.75 QALYs, semaglutide 10.48 QALYs, and tirzepatide 10.68 QALYs. Estimated lifetime costs were $222,300, $226,300, $273,500, and $280,00, respectively. Incremental analysis showed that adding diet and exercise to UC resulted in an incremental cost-effectiveness ratio (ICER) of $25,400 per QALY, while the ICER associated with adding tirzepatide was $57,400 per QALY. One-way sensitivity analyses showed that the ICER of tirzepatide varied the most with changes in weight loss efficacy and treatment costs. For example, tirzepatide was less clinically effective and more costly than semaglutide when its BMI reduction was 50-75% of the base case. Tirzepatide’s ICER increased to $153,800 per QALY when using Federal Supply Schedule costs; it also increased when the cohort BMI was lowered to 33 kg/m² or when ability to reduce risk of major adverse cardiovascular events was removed. Probabilistic sensitivity analyses showed that with a cost-effectiveness threshold of $100,000 per QALY, tirzepatide was cost-effective in 64% of simulations and semaglutide in 34%. Overall, this study suggests that both tirzepatide and semaglutide may be cost-effective for the treatment of knee osteoarthritis in patients with obesity.

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