Cost-Effectiveness of Pharmacologic Treatments in Adults With Overweight or Obesity: A Systematic Review for the American College of Physicians.

BACKGROUND: A comprehensive overview of the cost-effectiveness of pharmacologic treatments for overweight or obesity is lacking. PURPOSE: To evaluate cost-effectiveness of pharmacologic treatments in adults with overweight or obesity in a U.S. setting. DATA SOURCES: MEDLINE, Embase, and economic databases, searched on 13 October 2025. STUDY SELECTION: Non-industry-sponsored U.S. trial-based and model-based cost-effectiveness evaluations of pharmacologic treatments in adults with overweight or obesity. DATA EXTRACTION: Data on clinical characteristics, economic characteristics (for example, model type), and study outcomes were extracted by one reviewer and verified by a second reviewer. Study quality was assessed using the CHEQUE (Criteria for Health Economic Quality Evaluation) tool; value was assessed using incremental cost-effectiveness ratios (ICERs), with thresholds for high value (<$100 000 per quality-adjusted life-year [QALY], or dominant), intermediate value ($100 000 to $200 000 per QALY), low value (>$200 000 per QALY), and no value (strict or extended dominance, or less costly and less effective); and certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. DATA SYNTHESIS: Four out of 9 included studies were at low risk of bias. None of the 42 pairwise comparisons that were reported had high certainty. In the 6 studies with moderate certainty, liraglutide had low value and phentermine-topiramate and tirzepatide had high value when each was compared with lifestyle modification. Semaglutide had low value compared with naltrexone-bupropion and phentermine-topiramate and high value compared with liraglutide. LIMITATIONS: All studies were model-based. ICERs were not reported for all potential treatment comparisons. Most studies had incomplete reporting or were at high risk of bias. CONCLUSION: Current evidence on cost-effectiveness of pharmacologic treatment of overweight or obesity is hampered by poor-quality studies, limiting the ability to draw conclusions. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42023491646).