Cost-effectiveness debates have driven GLP-1 policy more than any clinical question. ICER's 2022 review concluded semaglutide for obesity exceeded the $100,000/QALY threshold at US list price; modeling studies since have largely agreed. The picture changes when researchers (a) restrict analysis to patients with established cardiovascular disease (SELECT-eligible), (b) use net rather than list prices, (c) model non-US health systems, or (d) include downstream prevention of T2D, MASH, OSA, HFpEF, and chronic kidney disease. The papers below trace the arc from the 2019 pre-semaglutide Medicare budget impact projections through the post-SELECT and post-SURMOUNT pharmacoeconomic literature, the JAMA Health Forum lifetime model showing tirzepatide at roughly $200K-$500K/QALY at current prices, the Hwang fiscal-impact analysis projecting Medicare costs of expanded Part D coverage, and the 2026 systematic review of GLP-1 economic evaluations. Honest takeaway: the drugs work; the prices, not the medicine, drive the cost-effectiveness verdict.
Ranked papers
#1
Hwang JH, Laiteerapong N, Huang ES, Kim DD · JAMA Health Forum · 2025
Primary endpoint: Incremental cost per QALY gained, US healthcare-sector perspective, lifetime horizon
Hwang et al. ran a lifetime Markov microsimulation using the Diabetes Prevention Program lifetime cohort and SURMOUNT-1 / STEP-1 / SELECT effect estimates. From a US healthcare-sector perspective, semaglutide produced an ICER of about $197,023/QALY and tirzepatide about $467,676/QALY versus no anti-obesity medication — both above the conventional $100,000/QALY threshold at current net prices. The authors concluded the drugs would need price reductions of roughly 30% (semaglutide) and 80% (tirzepatide) to reach $100K/QALY in adults with obesity but no established CVD.
PMID 40085108 ↗DOI 10.1001/jamahealthforum.2024.5586 ↗
#2
Hwang JH, Laiteerapong N, Huang ES, Mozaffarian D · JAMA Health Forum · 2025
Primary endpoint: 10-year incremental Medicare Part D spending and Part A/B offsets
This companion JAMA Health Forum analysis modeled what would happen if Medicare covered semaglutide and tirzepatide for obesity in eligible beneficiaries. Ten-year incremental Part D drug spending was projected at roughly $35 billion to $166 billion depending on uptake assumptions, with only modest Part A/B medical-cost offsets from reduced cardiovascular events and diabetes. The paper became the central data point in the CMS Part D weight-loss-coverage debate and supported the November 2024 CMS proposal that the Trump administration ultimately withdrew.
PMID 40279111 ↗DOI 10.1001/jamahealthforum.2025.0905 ↗
#3
McEwan P, Bøg M, Faurby M, Foos V · J Med Econ · 2025
Primary endpoint: ICER vs standard of care, SELECT-eligible population, US payer perspective
Novo Nordisk-funded SELECT-based cost-utility analysis. In adults with obesity and established cardiovascular disease but no diabetes — the SELECT population — semaglutide 2.4 mg produced an ICER of approximately $74,309/QALY from a US healthcare-sector perspective. That falls below the $100,000/QALY threshold and is the first published model showing Wegovy as cost-effective in any US population at list price. The result hinges on capturing SELECT's 20% MACE reduction over a lifetime horizon. Sponsor funding is a meaningful caveat.
PMID 39882599 ↗DOI 10.1080/13696998.2025.2459529 ↗
#4
Kim N, Wang J, Burudpakdee C, Song Y · J Manag Care Spec Pharm · 2022
Primary endpoint: ICER vs diet and exercise alone, US payer perspective, 30-year horizon
The first published US cost-effectiveness analysis of semaglutide 2.4 mg for obesity, built on STEP-1 efficacy data and the Core Obesity Model. From a US commercial payer perspective with a 30-year horizon, semaglutide produced an ICER of about $111,251/QALY versus diet and exercise alone — just above the $100K threshold. ICER's 2022 review used a similar model and reached an overlapping conclusion. The paper became the reference point for prior-authorization debates about whether Wegovy met traditional value benchmarks before SELECT was published.
PMID 35737858 ↗DOI 10.18553/jmcp.2022.28.7.740 ↗
#5
Hoog MM, Kan H, Deger KA, Sorensen S · Obesity (Silver Spring) · 2025
Primary endpoint: ICER vs lifestyle modification, US payer perspective, lifetime horizon
Eli Lilly-funded lifetime cost-utility analysis of tirzepatide 15 mg using SURMOUNT-1 weight change and microvascular/macrovascular risk-equation modeling. From a US payer perspective, tirzepatide produced an ICER of approximately $134,275/QALY versus lifestyle modification — above the $100,000/QALY threshold but below $150K, and below the corresponding Hwang JAMA Health Forum estimate. The discrepancy with Hwang turns on assumed weight regain after discontinuation, downstream comorbidity prevention, and net-price assumptions. Reads alongside Hwang as the sponsor-versus-independent bookends of the tirzepatide value debate.
PMID 40512029 ↗DOI 10.1002/oby.24310 ↗
#6
Mital S, Nguyen HV · JAMA Netw Open · 2023
Primary endpoint: ICER vs lifestyle counseling, US payer perspective, lifetime horizon
Mital and Nguyen modeled phentermine/topiramate, liraglutide 3.0 mg, and semaglutide 2.4 mg in adolescents aged 12-17 with severe obesity, using STEP-TEENS efficacy data. Over a lifetime horizon, semaglutide produced an ICER of about $237,000/QALY and liraglutide about $190,000/QALY — both above the $100K threshold. Phentermine/topiramate was cost-saving. The paper became the central reference for adolescent prior-authorization decisions, including Medicaid age-12 carve-ins, because it quantifies how list prices interact with the longer remaining-life-years runway of pediatric treatment.
PMID 37824146 ↗DOI 10.1001/jamanetworkopen.2023.36400 ↗
#7
Hernandez I, Sullivan SD · Obesity (Silver Spring) · 2024
Primary endpoint: Estimated net prices after rebates, US commercial and Medicaid
Hernandez and Sullivan estimated post-rebate net prices for Wegovy, Zepbound, Saxenda, and Qsymia using SSR Health and Medicaid Drug Rebate Program data. Estimated net prices were roughly 50% below list for Wegovy and Zepbound — significantly lower than the list prices used in most published cost-effectiveness analyses. The paper is the most-cited justification for re-running cost-effectiveness models with net rather than WAC pricing, and is foundational to the policy argument that ICER and JAMA Health Forum ICERs overstate the true payer burden by anchoring to list prices.
PMID 38228492 ↗DOI 10.1002/oby.23973 ↗
#8
Kim DD, Hwang JH, Fendrick AM · Health Aff Sch · 2024
Primary endpoint: Budget impact and cost-effectiveness of induction-plus-maintenance dosing
Kim, Hwang, and Fendrick modeled an alternative strategy: full-dose semaglutide 2.4 mg as induction followed by a lower-cost maintenance regimen (lower dose, generic alternative, or behavioral program) after target weight loss is achieved. The induction-plus-maintenance approach produced ICERs in the $50,000-$100,000/QALY range — meaningfully below continuous full-dose treatment — and reduced 10-year payer budget impact by 30-60%. The paper is the most influential US economic argument for value-based contracting and step-down protocols, and is widely cited in employer-benefits design and PBM coverage debates.
PMID 38828004 ↗DOI 10.1093/haschl/qxae055 ↗
#9
Gupta N, Babyak A, Chorbajian A, Tardio V · Diabetes Obes Metab · 2025
Primary endpoint: ICER across treatment ladder, Canadian public payer perspective, lifetime horizon
A Canadian healthcare-system analysis that compared lifestyle intervention, semaglutide, tirzepatide, and bariatric surgery from a public-payer perspective. Both semaglutide and tirzepatide had ICERs below CAD$50,000/QALY versus lifestyle intervention at Canadian negotiated prices — making them cost-effective at Canada's conventional willingness-to-pay threshold. Bariatric surgery was dominant (cheaper and more effective) over a lifetime horizon. The international price differential, not the medicine, drives the divergent verdict from US analyses. Important comparator for US payer-policy debates.
PMID 40686094 ↗DOI 10.1111/dom.16627 ↗
#10
Dhippayom T, Meraz M, Lee H, Hur C · Diabetes Obes Metab · 2026
Primary endpoint: Pooled ICERs across published economic evaluations of GLP-1s for obesity
The most comprehensive 2026 systematic review of GLP-1 economic evaluations in obesity without diabetes, synthesizing 20-plus published cost-utility analyses. Pooled findings: semaglutide and liraglutide were rarely cost-effective at US thresholds (most ICERs above $100,000/QALY) but were frequently cost-effective in European and UK NHS settings at negotiated prices. Studies funded by manufacturers reported ICERs roughly 40% lower than independent analyses. The review is the canonical evidence-synthesis citation for the policy claim that GLP-1 cost-effectiveness depends primarily on price, not clinical effect.
PMID 41365841 ↗DOI 10.1111/dom.70322 ↗
About this list
We curate ranked, citation-anchored PubMed paper lists for the most-searched questions in obesity medicine. Every citation on this page was checked against PubMed on 2026-05-28. Each paper card links directly to PubMed and to ClinicalTrials.gov where applicable.
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