Topline Findings
- Significant Weight Loss Achieved: Zepbound delivers 17.8%–20.8% average weight loss, while injectable Wegovy achieves 14%–17%, and oral Wegovy 11.4%, highlighting effective obesity management options.
- Cost-Effectiveness Highlighted: All therapies are highly cost-effective at conventional thresholds, with QALY estimates of $53,400 for tirzepatide, $61,400 for injectable semaglutide, and $69,300 for oral semaglutide.
- Access and Affordability Challenges: Despite strong clinical benefits, fewer than 1% of eligible US adults are able to afford GLP-1 treatments at current net prices, emphasizing the need for broader coverage and policy solutions.
The Institute for Clinical and Economic Review (ICER) has released a Draft Evidence Report evaluating the comparative clinical effectiveness and value of Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide) for obesity management, including their impact on other obesity-related outcomes. ICER stated that the preliminary draft represents the midpoint of its eight-month assessment process and should not be interpreted as the organization’s final conclusions.1
How Effective and Cost-Efficient are the Newest Obesity Treatments?
Key Clinical Findings
- The initial draft found that both agents, when added to lifestyle modification, produced significant weight loss, improvements in obesity-related comorbidities, and reductions in cardiovascular risk factors.
- Zepbound demonstrated the greatest weight loss benefits, with average weight loss ranging from 17.8% to 20.8%, and a head-to-head trial showing 20.2% loss versus 13.7% with injectable Wegovy. Early topline results in diabetes populations also suggest promising cardiovascular benefits, including an 8% reduction in major adverse cardiovascular events and a 16% reduction in all-cause mortality.
- Injectable Wegovy demonstrated sustained weight loss of 14% to 17% and provided clear cardiovascular benefit, lowering major adverse cardiovascular events by 20% and all-cause mortality by 19% in patients with established cardiovascular disease.
- Oral Wegovy also proved effective, producing an 11.4% average reduction, though with somewhat less impact than the injectable form, raising questions about its long-term cardiovascular benefits.
- Safety profiles were largely consistent across medications.
- The most common adverse events (AEs) were gastrointestinal, including nausea, diarrhea, and constipation, affecting up to 75% of patients treated with Zepbound and 20%–40% of patients treated with Wegovy.
- Overall discontinuation due to AEs was below 10%.
Cost-Effectiveness and Affordability
- The analysis found all three medications to be highly cost-effective at conventional thresholds.
- Incremental cost-effectiveness ratios were estimated at $53,400 per quality-adjusted life year gained for tirzepatide, $61,400 for injectable semaglutide, and $69,300 for oral semaglutide.
- Despite favorable cost-effectiveness, ICER projected affordability concerns: at current net prices of $6,830 for semaglutide and $7,973 for tirzepatide, fewer than 1% of eligible adults in the United States could be treated before surpassing ICER’s budget impact threshold of $880 million annually.
Obesity Treatment Access Considerations
In the United States, the current estimated prevalence of obesity is around 40%, with no significant differences found between men and women across all age groups.2,3
“Despite the number of therapies available, there remain challenges to accessing highly effective obesity medications and thus additional options for treatment may be beneficial in closing the treatment gap,” explained the authors of the report.
The report concluded that both treatments provide meaningful clinical benefits, with Zepbound achieving the most significant weight loss and Wegovy demonstrating established cardiovascular protection. Both were determined to be highly cost-effective but pose serious affordability and access challenges if broadly adopted.1
Next Steps and Stakeholder Engagement
As part of its Early Insights Webinar Series, David Rind, CEO, ICER, is expected to present the initial findings on September 18, 2025, in a webinar available exclusively to ICER Analytics platform users. The final report will be discussed during a virtual public meeting of the New England Comparative Effectiveness Public Advisory Council on November 13, 2025, during which the independent council will vote on key questions from the report.1
References
- Institute for Clinical and Economic Review Releases Draft Evidence Report on Treatments for Obesity. ICER. September 10, 2025. Accessed September 10, 2025. https://icer.org/news-insights/press-releases/institute-for-clinical-and-economic-review-releases-draft-evidence-report-on-treatments-for-obesity/
- Semaglutide and Tirzepatide for Obesity Effectiveness and Value. ICER. Accessed September 10, 2025. https://icer.org/wp-content/uploads/2025/09/ICER_Obesity_Draft-Report_For-Publication_090925.pdf
- Obesity and Severe Obesity Prevalence in Adults: United States, August 2021–August 2023. CDC. Accessed September 10, 2025. https://www.cdc.gov/nchs/products/databriefs/db508.htm#:~:text=2021%E2%80%93August%202023-,1,59%2C%20and%2060%20and%20older.
