The Institute for Clinical and Economic Review (ICER) has significantly revised its stance on GLP-1 drugs for obesity treatment, concluding that blockbuster medications from Novo Nordisk and Eli Lilly offer substantial health benefits and represent cost-effective treatment options. This marks a dramatic shift from ICER's 2022 assessment, which found the drugs were not cost-effective compared to lifestyle changes alone.
The updated analysis evaluated three formulations: injectable semaglutide (Wegovy), oral semaglutide currently under FDA review, and injectable tirzepatide (Zepbound). All drugs were assessed at maximum doses for weight loss in adults with obesity or overweight status and at least one related comorbidity, excluding patients with Type 2 diabetes.
Significant Weight Loss and Health Benefits
The analysis revealed substantial weight loss across all three medications compared to placebo. Tirzepatide demonstrated the greatest efficacy with a mean weight difference of -17.8%, followed by injectable semaglutide at -13.1% and oral semaglutide at -11.4%. Head-to-head trials confirmed tirzepatide's superior weight loss compared to semaglutide.
"Because treatment with all three drugs results in substantial weight loss and improvement in metabolic risk factors, we have high certainty that all three drugs have substantial net health benefit over lifestyle modifications alone," the report stated.
Beyond weight reduction, all three drugs improved health-related quality of life and metabolic risk factors including blood pressure, blood glucose, and lipids. The medications also demonstrated fewer cardiovascular events, contributing to their overall clinical value.
Cost-Effectiveness Analysis
Using quality-adjusted life years (QALYs) as the evaluation metric, ICER found all three drugs met its $100,000 per QALY threshold. Tirzepatide emerged as the most cost-effective option at approximately $53,000 per QALY gained, followed by injectable semaglutide at $61,000 and oral semaglutide at $69,000.
The analysis used estimated net prices from SSR Health of $6,830 for Wegovy and $7,973 for Zepbound, with oral semaglutide assumed to match Wegovy's pricing.
Budget Impact Concerns
Despite meeting cost-effectiveness thresholds, the drugs' high prices create significant affordability challenges. ICER estimated that treating fewer than 1% of eligible patients would exceed its annual budget impact threshold of $880 million. With up to 40% of the U.S. population potentially eligible for GLP-1 treatment for obesity, payers face enormous budget pressures.
A PwC survey from October 2024 found that 8% to 10% of Americans are currently taking GLP-1 drugs, with 30% to 35% expressing interest in using them. This growing demand has prompted employers to link rising insurance costs to GLP-1 usage, with many adding authorization requirements or avoiding obesity coverage altogether.
Treatment Challenges and Adherence
Maintaining patients on treatment remains challenging, with those who discontinue regaining weight and losing metabolic improvements. Dr. David Rind, ICER's chief medical officer, emphasized that GLP-1 drugs should be considered chronic therapies similar to statins rather than short-term interventions.
"We don't have any evidence that these drugs can be taken for a period of time to lose weight and then stopped," Rind explained. "We certainly don't know if the large benefits that you get from these drugs on cardiovascular endpoints are maintained if patients stop taking them."
Gastrointestinal side effects present another adherence challenge. Three-quarters of patients taking injectable or oral semaglutide reported gastrointestinal symptoms, while 20% to 40% of Zepbound patients experienced nausea, diarrhea, or constipation in clinical trials.
Clinical Perspective on Obesity Treatment
Rind described obesity as partly a disorder of brain "set points" that drive persistent hunger signals, which GLP-1s appear to reset, enabling sustained weight loss. "We know tirzepatide works better and has likely fewer side effects than semaglutide, but to be able to say which is the better drug for cardiovascular disease, we don't really know yet," he noted.
The analysis acknowledges that real-world outcomes may differ from clinical trial results, as trial participants typically demonstrate better adherence and outcomes due to closer monitoring and support.
ICER will accept comments on the draft until October 6, 2025, with the evidence report issued October 29 and the final report available December 19, 2025. While ICER reports don't set policy, they significantly influence payer coverage decisions and drug pricing negotiations.
