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BOSTON, October 29, 2025 – The Institute for Clinical and Economic Review (ICER) today posted its revised Evidence Report assessing the comparative clinical effectiveness and value of semaglutide (injectable Wegovy®, and a yet to be approved oral formulation) (Novo Nordisk) and tirzepatide (Zepbound®) (Eli Lilly and Company) for the treatment of obesity. ICER is also assessing how these treatments affect additional obesity-related outcomes.
“Over the past few years, semaglutide and tirzepatide have revolutionized the management of obesity,” said ICER’s Chief Medical Officer, David Rind, MD, MSc. “In addition to typically producing meaningful weight loss, these therapies reduce cardiovascular risk and improve multiple other aspects of the metabolic syndrome as well as additional obesity-related conditions.”
This Evidence Report will be reviewed at a virtual public meeting of the New England CEPAC on November 13, 2025. The New England CEPAC is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.
Register here to watch the live webcast of the virtual meeting.
A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.
Key Clinical Findings
When compared with lifestyle modifications, ICER assigned a rating of A for injectable semaglutide, oral semaglutide, and tirzepatide. When tirzepatide was compared with injectable semaglutide or oral semaglutide, ICER assigned a rating of P/I. Oral semaglutide was assigned a C- rating when compared to injectable semaglutide.
Tirzepatide produces more weight loss than oral or injectable semaglutide. However, because of yet to be answered questions about relative cardiovascular benefits, there is some uncertainty about the comparative effectiveness of the three drugs when all outcomes are considered.
Key Cost-Effectiveness Findings
ICER evaluated the cost-effectiveness of injectable semaglutide, oral semaglutide and tirzepatide. Injectable semaglutide has a current estimated net price of $6,829, while tirzepatide is priced at $7,973. Oral semaglutide has not yet been approved by the FDA for obesity, and manufacturer has not yet announced a US price for the therapy if approved. For the purposes of our assessment, it was assumed that the net price is the same as injectable semaglutide.
ICER has calculated a health benefit price benchmark (HBPB) to be between $9,100 and $12,500 for injectable semaglutide, $8,300 and $11,400 for oral semaglutide, and $11,500 and $15,800 for tirzepatide.
In 2022, ICER’s review found that semaglutide would achieve common thresholds for cost-effectiveness if priced between $7,500 – $9,800 per year after rebates. Evidence of improved clinical benefits for patients in the years since that review have in part led to the updated price.
Despite the high cost-effectiveness of these treatments, there are serious affordability concerns. ICER estimates that fewer than 1% of eligible patients could be treated at current and assumed net prices before crossing the ICER budget impact threshold of $880 million annually.
ICER’s HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, net of all rebates and discounts, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.
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