Tirzepatide more cost-effective than semaglutide in patients with knee osteoarthritis and obesity

Embargoed for release until 5:00 p.m. ET on Monday 15 September 2025   

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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.   
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1. Tirzepatide more cost-effective than semaglutide in patients with knee osteoarthritis and obesity

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-03609

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03113  

URL goes live when the embargo lifts             

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 Orthopaedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital assessed 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 weigh 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.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Elena Losina, PhD please email Haley Bridger at hbridger@mgb.org. 

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2. Despite commercial availability, evidence of benefits, accuracy, and harms of multicancer detection tests is unclear

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-01877

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03530

URL goes live when the embargo lifts             

A systematic review assessed the benefits, accuracy, and harms of screening with blood-based multicancer detection (MCD) tests in asymptomatic adults. The review revealed that no controlled studies that report benefits of MCD test screening have been completed, and there was insufficient evidence to evaluate harms and accuracy. The findings can inform focus areas for additional research on MCD tests. The review is published in Annals of Internal Medicine. 

Researchers from RTI–University of North Carolina Evidence-Based Practice Center and The Ohio State University College of Medicine aimed to review and analyze controlled studies of MCD tests in asymptomatic populations reporting cancer detection, mortality, quality of life, and harms (psychosocial, adverse events, decrease in standard-of-care screening); uncontrolled studies for harms of diagnostic evaluation; and test accuracy studies completed between 1 January 2013 and 26 December 2024. The researchers did not identify any completed controlled studies of MCD tests for screening. For test accuracy, the researchers included 20 unique studies reporting on 19 unique MCD tests. They found that accuracy varied widely based on study design, type of cancer the MCD test was designed to report, and subgroups of participants. One controlled study reported on one harm of screening outcome and two harms of diagnostic evaluation outcomes; however; the strength of the evidence reported was deemed insufficient due primarily to study limitations and unknown or inconsistent findings. Despite limited or insufficient evidence to support the widespread adoption of MCD tests, some tests are commercially available. To address gaps in knowledge, the reviewers say future research should include empirical studies on 1) surrogate outcomes for cancer-specific mortality, 2) benefits and harms of MCD tests in various populations, 3) harms and cost-effectiveness, 4) the optimal timing of use and intervals for rescreening, and 5) communicating benefits and risks for screening with MCD tests to clinicians and patients. Results from this review can inform clinical and policy decision making by clinicians, medical professional organizations, guideline developers, health care payers, and other groups or organizations. 

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Leila C. Kahwati, MD, MPH please email news@rti.org.  

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