Tirzepatide More Cost-Effective Than Semaglutide for Obesity and Knee Osteoarthritis

Glucagon-like peptide-1 receptor agonist (GLP-1) tirzepatide is more cost-effective than semaglutide for patients with knee osteoarthritis (OA) and obesity, a new study reported in the Annals of Internal Medicine.1

Knee OA affects nearly 30 million US adults and 370 million people worldwide. The risk for knee OA increased in individuals with obesity, often resulting in an earlier diagnosis of knee OA and presenting with more severe pain and functional limitations when compared to those without obesity. OA is also associated with diabetes, which can potentially increase the risk of early mortality. Patients with obesity and osteoarthrosis have a higher mortality rate, which is likely due to systemic inflammatory status, comorbidities, and mobility limitations.2

Tirzepatide is more cost-effective than semaglutide for patients with obesity and osteoarthritis. | Image Credit: @Miha Creative-AdobeStock.jpeg

Weight loss through intervention—such as lifestyle changes (diet and exercise), pharmaceuticals, and bariatric surgery—can reduce knee joint loading, systemic inflammation, and knee pain. Although bariatric surgery can provide more substantial weight loss and is less likely to lead to remission or weight gain recurrence, the increased use of GLP-1s has been shown to reduce knee pain in patients with OA. However, cost factors can influence patient decisions, as modeled in this new study, which discusses the most cost-effective options for treating obesity in patients with OA.

The study found that tirzepatide had a $57,400 per lifetime quality-adjusted life-years (QALYs) threshold—the quantity (life years gained) and quality (health-related quality of life) of health outcomes—when compared to semaglutide. These data show that tirzepatide provided greater clinical benefits at a lower cost when assessed for lifelong use compared with semaglutide.1

What is a Cost-Effectiveness Threshold?

Cost-effectiveness thresholds are predefined values to determine whether a health care intervention provides good value for its cost. These thresholds represent the maximum amount a payer (i.e., health insurance companies, government agencies—Medicaid and Medicare) is willing to pay for one additional unit of health benefit or QALY. If the incremental cost-effectiveness ratio (ICER) of a health care intervention (i.e., the additional cost divided by the additional health benefit) is below the threshold, then the intervention is considered cost-effective. Commonly accepted thresholds amongst payers for cost-effectiveness of $100,000 per QALY.

“Different payers have different cost-effectiveness thresholds, and for academic publishing, the commonly used cost-effectiveness ratio is $100,000 per QALY, but different payers may have different thresholds,” corresponding author Elena Losina, PhD, codirector of the Orthopedics and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital, said in an interview with The American Journal of Managed Care®. “So, what we as scientists do is provide policymakers data that is, we hope, useful for making their coverage decisions.”

The Osteoarthritis Policy (OAPol) Model was used to assess the cost-effectiveness of semaglutide, tirzepatide, and other common weight loss interventions in patients with obesity and knee osteoarthritis. The model is designed to simulate disease progression, treatment effects, associated costs, and QALY over a patient’s lifetime. To generate long-term health and economic outcomes, the model also applied factors such as patient-identified weight change, pain relief, disease progression, and adverse events.

Of participants, the mean age was 56 years, 81.6% of whom were women, 88.9% of whom were non-Hispanic White, and the mean BMI was 40.3 kg/m².

Cost-Effectiveness Threshold Comparisons

The primary analysis focused on nonsurgical options from a health care perspective. Usual care, or UC (i.e., physical therapy, pain management, lifestyle changes, and possible medications), amounted to 9.5 QALY compared with 9.75 for diet and exercise. The lifetime costs for diet and exercise, semaglutide, and tirzepatide were estimated at $226,300, $273,500, and $273,500, respectively, and $222,300 for UC. When diet and exercise were added to UC and analyzed incrementally, the ICER was $25,400 per QALY—which is representative of a more conservative approach where only cost-effective strategies are adopted. Furthermore, tirzepatide for UC resulted in a $57,000 ICER. While higher, it demonstrates payers’ willingness to pay more per QALY.

On the other hand, the secondary analysis, which was simulated to reflect a scenario in which all of the cohort was eligible for bariatric surgery, showed a significantly lower ICER of $20,600 per QALY, thus dominating diet and exercise and tirzepatide.

“You put the cost upfront for bariatric surgery, and you experience, or patients experience, benefits for a long period of time,” Losina said. “Comparing those two strategies, then, bariatric surgery shows that it provides better benefit without exceeding the cost-effectiveness threshold. That's why it is shown to be a cost-effective option for those patients who are eligible and willing.”

The study’s findings should be viewed with caution given several limitations. Long-term outcomes with GLP-1 receptor agonists remain uncertain, and assumptions about lifetime use, adherence, and costs may not reflect real-world patterns or future drug pricing. In addition, the model simplifies complex scenarios, has limited data on sustained weight loss in osteoarthritis, and may not fully generalize across patient populations or healthcare systems.

“Hopefully, this analysis may play a role in influencing some coverage decisions. The clinical decision-making should not be made solely on the cost-effectiveness ground,” Losina said. “There's such an important discussion that needs to be perceived by patients and their clinicians in one-to-one conversations.”

References

1. Betensky DJ, Smith KC, Katz JN, et al. The cost-effectiveness of semaglutide and tirzepatide for patients with knee osteoarthritis and obesity. Ann Intern Med. 2025(178):9 doi:10.7326/ANNALS-24-03609

2. McCormick B. Higher weight-adjusted waist index tied to greater mortality risk in patients with osteoarthritis. AJMC. April 22, 2025. Accessed September 12, 2025. https://www.ajmc.com/view/higher-weight-adjusted-waist-index-tied-to-greater-mortality-risk-in-patients-with-osteoarthritis

3. McCrear S. Bariatric surgery reduces metabolic comorbidities in patients with obesity. AJMC. September 9, 2025. Accessed September 12, 2025. https://www.ajmc.com/view/bariatric-surgery-reduces-metabolic-comorbidities-in-patients-with-obesity