What Does SURMOUNT-4 Tell Us About the Cost-Effectiveness of Long-Term Tirzepatide?

At a glance

| Parameter | Detail | |---|---| | Trial | SURMOUNT-4 (JAMA 2024) | | N | 670 (randomized at week 36) | | Intervention | Tirzepatide (10 or 15 mg) continuation vs switch to placebo | | Duration | 36-week open-label lead-in + 52-week randomized period (88 weeks total) | | Primary endpoint | Percent change in body weight from week 36 to week 88 | | Key result | Continuation: −5.5% additional loss; Placebo switch: +14.0% regain | | Economic relevance | Quantifies the cost of indefinite therapy against the cost of regain |

Why SURMOUNT-4 Changed the Economic Conversation

Before SURMOUNT-4, cost-effectiveness models for GLP-1 receptor agonists in obesity relied on assumptions about treatment duration. Most early models assumed a finite course (1 to 3 years), after which patients would retain some fraction of lost weight. SURMOUNT-4 destroyed that assumption. The 14% regain in the placebo-switch arm over just 52 weeks made clear that tirzepatide, like most obesity pharmacotherapy, requires indefinite use to maintain clinical benefit.

This single finding recalibrated every cost-effectiveness analysis (CEA) published before 2024. A two-year drug course costs roughly $24,000 at list price. A lifetime course for a 45-year-old could exceed $500 to 000 in undiscounted terms. The question is whether the clinical returns justify that spend.

List Price vs Net Price: The Number That Matters

Eli Lilly set the wholesale acquisition cost (WAC) for Zepbound (tirzepatide for obesity) at approximately $1,060 per month at launch in late 2023. That figure, however, overstates what most insured patients and payers actually pay.

| Price metric | Approximate monthly cost | Annual cost | |---|---|---| | WAC (list price) | $1,060 | $12,720 | | Estimated net price (after rebates) | $550, $700 | $6,600, $8,400 | | Patient copay (commercial, with coverage) | $25, $150 | $300, $1,800 | | Cash-pay / savings card | $550 (Lilly direct) | $6,600 |

The gap between list and net is significant for CEA modeling. Analyses using WAC consistently produce cost-per-QALY figures above $150,000. Those using estimated net prices land closer to $60,000, $100,000 per QALY, a range that falls within or near the commonly cited $100,000, $150,000 per QALY willingness-to-pay threshold used by U.S. decision-makers.

Published Cost-Effectiveness Models Drawing on SURMOUNT Data

The ICER 2022 to 2024 Assessments

The Institute for Clinical and Economic Review (ICER) published its initial assessment of tirzepatide for obesity in late 2023, updating it as SURMOUNT trial data accumulated. ICER's base-case model estimated a cost-effectiveness ratio of approximately $120,000, $170,000 per QALY at WAC for tirzepatide in adults with BMI ≥30. When ICER applied a health-benefit price benchmark aligned with a $100,000/QALY threshold, the suggested annual price dropped to roughly $7,500, $9,400, close to the estimated post-rebate net price.

Key assumptions in the ICER model:

• Treatment duration: Lifetime use, informed by the SURMOUNT-4 regain data
• Weight regain on discontinuation: Modeled at 65 to 80% regain within two years, consistent with SURMOUNT-4's 52-week trajectory extrapolated forward
• Comorbidity offsets: Included reductions in type 2 diabetes incidence, cardiovascular events, and knee replacement, drawing on the SURMOUNT-1 through SURMOUNT-4 comorbidity data
• Discount rate: 3% annually for both costs and outcomes

Independent Academic Models (2024 to 2025)

Several academic groups published CEAs using SURMOUNT-4 continuation/discontinuation data as direct inputs. A Markov cohort model published in Obesity (2024) stratified results by baseline BMI and comorbidity count. For patients with BMI ≥35 and at least two obesity-related comorbidities (type 2 diabetes, hypertension, obstructive sleep apnea), the incremental cost-effectiveness ratio (ICER, the metric, not the institute) dropped below $80,000 per QALY at net price. For patients with BMI 30, 35 and no comorbidities, the ratio exceeded $200,000 per QALY even at net price.

This stratification matters. It suggests that from a pure health-economic perspective, tirzepatide is most cost-effective in the patients who are sickest, not simply the heaviest.

The Regain Problem as an Economic Variable

The SURMOUNT-4 placebo-switch arm showed that participants regained an average of 14% body weight in 52 weeks after stopping tirzepatide at week 36. Continuation participants lost an additional 5.5%, creating a net difference of roughly 19.5 percentage points.

For economic modeling, the regain trajectory is the most influential input variable. Small changes in assumed regain rate produce large swings in lifetime cost-effectiveness:

| Assumed regain on discontinuation (2-year) | ICER at net price ($/QALY) | ICER at WAC ($/QALY) | |---|---|---| | 50% regain | ~$130,000 | ~$220,000 | | 75% regain (base case) | ~$80,000 | ~$150,000 | | 100% regain | ~$55,000 | ~$110,000 |

Paradoxically, the worse the regain, the more cost-effective continuation therapy appears, because the alternative (stopping) destroys more clinical value. SURMOUNT-4's 52-week data sits closer to the 75 to 100% regain range when extrapolated, which strengthens the economic case for continuation.

What Payers Are Actually Doing

Despite moderately favorable CEA results at net price, payer coverage for tirzepatide (Zepbound) remains inconsistent across the U.S. market.

Commercial plans: Roughly 40 to 50% of commercially insured lives had some access to GLP-1 agonists for obesity by early 2025. Prior authorization requirements are near-universal, typically requiring documented BMI ≥30 (or ≥27 with comorbidity), failure of lifestyle modification, and sometimes failure of older agents like phentermine.

Medicare Part D: As of early 2026, Medicare does not cover anti-obesity medications. The Treat and Reduce Obesity Act has been introduced repeatedly in Congress but has not passed. CMS estimated that adding GLP-1 coverage could cost $25, $50 billion over 10 years, a figure that reflects both the eligible population size and the chronic-use reality confirmed by SURMOUNT-4.

Medicaid: Coverage varies by state. Fewer than 15 state Medicaid programs covered GLP-1 agonists for obesity as of mid-2025. Several states that initially covered them imposed quantity limits or step-therapy requirements.

Employer self-insured plans: This segment has shown the most rapid adoption, driven by employers calculating that reduced diabetes, cardiovascular events, and disability costs offset some or all of the drug spend. Large employers like JPMorgan Chase and Walmart publicly disclosed GLP-1 coverage expansions in 2024 to 2025.

The Individual Value Calculation

For an individual patient, the relevant economic question is not the population-level ICER. It is: "Given my health profile, what am I gaining per dollar spent?"

SURMOUNT-4 provides concrete inputs for this calculation. A patient who responds to tirzepatide during an initial 36-week course (the open-label phase produced ~21% mean weight loss) and who would face ~14% regain over the following year if they stopped can estimate:

• Annual drug cost: $6,600, $12,720 depending on insurance and price tier
• Annual clinical benefit of continuation: Maintained ~21% total body weight loss rather than partial regain to ~18% loss (net ~3% at one year), plus the additional 5.5% loss seen with continuation
• Comorbidity offsets: Reduced or eliminated type 2 diabetes medications ($2,000, $15,000/year), reduced antihypertensive burden, reduced sleep apnea device costs ($1,000, $3,000/year), and potential surgical avoidance (bariatric surgery: $20,000, $35,000)

For patients with multiple comorbidities that improve with sustained weight loss, the net cost of tirzepatide therapy may be partially or fully offset within the first two to three years. For patients whose primary concern is cosmetic or whose comorbidity burden is low, the value proposition is weaker from a strictly economic standpoint.

Limitations of Current Economic Models

Every published CEA for tirzepatide carries significant uncertainty, and the authors of these models acknowledge several limitations:

Short follow-up extrapolated long: SURMOUNT-4 provides 52 weeks of randomized data. Lifetime models extrapolate 30 to 40 years from this. The assumption that regain rates remain constant is unvalidated.

Cardiovascular outcome data pending: The SURPASS-CVOT and SELECT-like trials for tirzepatide had not fully reported at the time most CEAs were conducted. If tirzepatide shows cardiovascular mortality reduction comparable to semaglutide in SELECT, cost-effectiveness ratios would improve substantially. Early signals from the SURMOUNT-MMO trial are expected by late 2026.

No head-to-head economic comparison: No CEA has directly compared tirzepatide to semaglutide 2.4 mg (Wegovy) using randomized head-to-head efficacy data, because no such trial exists. Cross-trial comparisons suggest tirzepatide produces greater weight loss (~21% vs ~15%), but the price differential is small, making the relative value calculation uncertain.

Productivity and quality-of-life gains underestimated: Most models capture direct medical costs but poorly capture productivity gains, reduced disability claims, and improvements in health-related quality of life. Patient-reported outcome data from SURMOUNT-4 showed sustained improvements in physical functioning scores with continuation, but translating these into economic terms remains imprecise.

Where the Economics Land

The economic case for tirzepatide continuation after SURMOUNT-4 is strongest for patients with high comorbidity burdens, when analyzed at net (not list) price, and when cardiovascular benefit assumptions are included. It is weakest for low-comorbidity patients at list price with short time horizons. Payer behavior reflects this gradient: coverage is expanding but remains conditional, prior-authorization-heavy, and absent from Medicare. The data from SURMOUNT-4 did not make tirzepatide cheap. It made the cost of stopping measurable, and that measurement is what drives every economic model forward.

Frequently asked questions

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References

1. Aronne LJ, Sattar N, Horn DB, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48. https://jamanetwork.com/journals/jama/fullarticle/2814876
2. Institute for Clinical and Economic Review (ICER). Medications for obesity management: effectiveness and value. 2023-2024 assessment. https://icer.org/assessment/obesity-management-2022/
3. Zepbound (tirzepatide) prescribing information. Eli Lilly and Company. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217806s000lbl.pdf
4. Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness: the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796-797. https://pubmed.ncbi.nlm.nih.gov/25162885/
5. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232. https://pubmed.ncbi.nlm.nih.gov/37952131/