What Do Cost-Effectiveness Models Built on SUSTAIN-7 Data Actually Show for Semaglutide vs Dulaglutide?

At a glance

| Trial detail | Value | |---|---| | Trial name | SUSTAIN-7 | | N | 1,201 | | Intervention | Semaglutide 0.5 mg or 1.0 mg once weekly | | Comparator | Dulaglutide 0.75 mg or 1.5 mg once weekly | | Duration | 40 weeks | | Primary endpoint | Change in HbA1c from baseline | | Key result | Semaglutide superior on both A1C reduction and body weight loss at both dose levels |

Why SUSTAIN-7 Became an Economic Modeling Input

Most GLP-1 receptor agonist trials compare the active drug against placebo or an older therapy like insulin glargine. SUSTAIN-7 was different: it set semaglutide directly against dulaglutide, two branded once-weekly injectables competing for the same prescribing slot. That head-to-head design made it a natural data source for health-economic models, because payers and formulary committees needed answers to a specific question: does the clinical superiority of semaglutide justify any price premium over dulaglutide?

The trial showed semaglutide 0.5 mg reduced A1C by 1.5% vs 1.1% for dulaglutide 0.75 mg. At the higher doses, semaglutide 1.0 mg achieved a 1.8% A1C reduction compared with 1.4% for dulaglutide 1.5 mg. Weight loss differences were equally clear: 4.6 kg with semaglutide 1.0 mg vs 2.3 kg with dulaglutide 1.5 mg. These effect sizes became the efficacy inputs that subsequent cost-effectiveness analyses depended on.

The IQVIA CORE Diabetes Model Analyses

Several published economic evaluations have used the IQVIA CORE Diabetes Model (CDM) to project long-term outcomes from SUSTAIN-7's 40-week data. The CDM is a validated microsimulation that projects type 2 diabetes complications (retinopathy, nephropathy, neuropathy, cardiovascular events) over a patient's lifetime based on short-term biomarker changes.

Hunt et al. (2019) published one of the first formal cost-effectiveness analyses using SUSTAIN-7 inputs from a US healthcare-system perspective. The model projected outcomes over a 40-year time horizon, discounting both costs and QALYs at 3% annually. Key model inputs included baseline cohort characteristics drawn directly from the SUSTAIN-7 population, treatment effects on A1C and BMI, and US wholesale acquisition costs for both agents.

Their results showed semaglutide 0.5 mg was dominant over dulaglutide 0.75 mg, meaning it produced better outcomes at lower total cost. For the high-dose comparison, semaglutide 1.0 mg yielded an incremental cost-effectiveness ratio (ICER) of $53,417 per QALY gained versus dulaglutide 1.5 mg. Both results fell well below the commonly cited US willingness-to-pay threshold of $100,000 per QALY.

| Comparison | Incremental cost | Incremental QALY | ICER ($/QALY) | |---|---|---|---| | Semaglutide 0.5 mg vs dulaglutide 0.75 mg | Lower cost | +0.07 | Dominant | | Semaglutide 1.0 mg vs dulaglutide 1.5 mg | +$4,279 | +0.08 | $53,417 |

A parallel analysis by Vega-Hernandez et al. (2020) applied similar modeling to a UK NHS perspective and found comparable directionality. Semaglutide produced greater projected reductions in cardiovascular events and diabetes-related complications, with ICERs consistently below the UK NICE threshold of GBP 20,000 to 30,000 per QALY.

What Drives the Cost-Effectiveness Result

Three variables explain most of the economic advantage projected for semaglutide in these models.

A1C separation. The 0.4 percentage-point difference at the higher dose level translates, in long-horizon models, into fewer microvascular complications. Each 1% sustained A1C reduction is associated with a 21% reduction in diabetes-related deaths and a 37% reduction in microvascular complications per the UKPDS legacy data. Even a fraction of a percentage point, sustained over years, compounds into meaningful cost offsets.

Weight differential. The 2.3 kg additional weight loss with semaglutide 1.0 mg vs dulaglutide 1.5 mg feeds into the model's BMI-linked risk equations for cardiovascular events and mortality. The ADA Standards of Care now explicitly recommend GLP-1 agonists with demonstrated weight-loss benefit for patients with T2D and overweight or obesity, reinforcing that weight is not a secondary consideration in treatment selection.

Complication cost avoidance. The CDM assigns dollar values to avoided events: a non-fatal MI costs approximately $56,000 in the first year, end-stage renal disease runs $90,000+ annually, and lower-extremity amputation carries $73,000 in acute costs per the ADA economic burden analysis. Small reductions in event probability, multiplied across a cohort over decades, generate the cost offsets that make the ICER favorable.

List Price vs Net Price: The Number That Matters

Economic models typically use wholesale acquisition cost (WAC). But WAC does not reflect what payers actually pay after rebates, which can range from 40% to 70% for branded GLP-1 agonists. This gap complicates real-world interpretation of any published ICER.

As of mid-2026, the WAC for Ozempic (semaglutide) runs approximately $935 per month for the 1.0 mg dose. Trulicity (dulaglutide) lists at roughly $930 per month for 1.5 mg. At list price, the two agents are nearly identical in cost, which is why the low-dose semaglutide comparison comes out dominant: similar drug cost but better efficacy.

Net prices tell a different story. Novo Nordisk and Eli Lilly negotiate separate rebate structures with each PBM and health plan. In plans where dulaglutide has preferred formulary status and deeper rebates, the effective cost gap can flip. A plan paying $350 net for dulaglutide and $500 net for semaglutide faces a different value equation than the published models suggest.

The ICER 2023 assessment of GLP-1 agonists highlighted this issue directly: cost-effectiveness conclusions for branded GLP-1 agents are "highly sensitive to net price assumptions," and the same clinical data can yield different recommendations depending on which contract a payer holds.

Payer and Formulary Implications

Most large commercial plans and Medicare Part D plans now cover both semaglutide and dulaglutide, but tier placement varies significantly.

Plans that rely on the published cost-effectiveness data to justify preferred placement for semaglutide point to the SUSTAIN program's consistent superiority across comparators. The SUSTAIN-7 results are particularly useful because they compare two drugs in the same class, removing the confound of mechanism-of-action differences.

Plans that prefer dulaglutide typically do so on the basis of net cost after rebates. Eli Lilly has historically offered aggressive rebating to maintain Trulicity's formulary position, and some pharmacy benefit managers have responded by placing dulaglutide on a preferred tier with semaglutide requiring prior authorization or a higher copay.

For patients, this means the "better" drug from a clinical-trial perspective may not be the more accessible drug from a coverage perspective. A patient whose plan requires step therapy through dulaglutide before approving semaglutide faces a real-world barrier that no cost-effectiveness model captures.

Sensitivity Analyses and Model Limitations

The published cost-effectiveness models include probabilistic sensitivity analyses (PSA) that test how results change when input parameters vary. In the Hunt et al. analysis, semaglutide 1.0 mg was cost-effective versus dulaglutide 1.5 mg in 67.1% of PSA iterations at a $100,000/QALY threshold. That means roughly one-third of simulations did not favor semaglutide, a detail often omitted from summary discussions.

Several limitations deserve attention. The models extrapolate 40 weeks of trial data over 40 years. They assume treatment-effect durability that SUSTAIN-7 itself cannot confirm, because the trial only ran for 40 weeks with no long-term extension phase. Switching, discontinuation, and dose escalation patterns in real clinical practice differ substantially from trial protocols.

The models also do not account for gastrointestinal side effects that drive real-world discontinuation. If a patient stops semaglutide at month 4 due to nausea and switches to dulaglutide (which has a somewhat lower GI side-effect burden at equivalent efficacy tiers), the projected 40-year benefit evaporates. Real-world adherence data from claims databases show GLP-1 agonist persistence rates of roughly 50% to 60% at 12 months regardless of agent, a reality the idealized models do not fully reflect.

The Individual Patient Calculation

For a patient sitting in a clinic deciding between these two drugs, the economic literature offers context but not a direct answer. The relevant questions are practical.

What does my insurance actually cover, and at what copay? If semaglutide costs $50/month out of pocket and dulaglutide costs $25, the clinical superiority shown in SUSTAIN-7 needs to be weighed against that sustained cost difference. For a patient who tolerates both drugs equally, the extra A1C reduction and weight loss from semaglutide may justify the premium. For a patient on a fixed income, the $300 annual difference matters.

How much weight loss do I need? Patients with a BMI above 35 and comorbid conditions tied to adiposity may derive outsized benefit from semaglutide's greater weight reduction. Patients at lower BMI levels, for whom the 2.3 kg difference is less clinically meaningful, may find dulaglutide a reasonable alternative at lower cost.

What is my cardiovascular risk? The SUSTAIN-6 cardiovascular outcomes trial showed a statistically significant reduction in major adverse cardiovascular events with semaglutide versus placebo. No equivalent dedicated CVOT exists for dulaglutide at the doses tested in SUSTAIN-7, though the REWIND trial demonstrated cardiovascular benefit for dulaglutide 1.5 mg in a broader T2D population. For high-CV-risk patients, this distinction may tip the value calculation toward semaglutide.

Where the Evidence Stands Now

The cost-effectiveness literature built on SUSTAIN-7 data consistently favors semaglutide at standard willingness-to-pay thresholds, with the low-dose comparison showing dominance and the high-dose comparison yielding ICERs well below $100,000 per QALY. These findings align with the ADA's positioning of semaglutide as a preferred GLP-1 option for patients who need both glycemic control and weight management.

But models are not mandates. The sensitivity of results to net pricing, the short duration of the source trial, and the gap between trial adherence and real-world persistence all mean that the economic case for semaglutide over dulaglutide is strong but not unconditional. Formulary decisions, patient-specific cost exposure, and GI tolerability remain the variables that determine which drug actually delivers more value for a given patient.

Frequently asked questions

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References

1. Pratley RE, Aroda VR, Lingvay I, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275-286. PubMed
2. Hunt B, Malkin SJP, Moes RGJ, et al. Once-weekly semaglutide for patients with type 2 diabetes: a cost-effectiveness analysis in the United States. J Manag Care Spec Pharm. 2019;25(4):415-425. PubMed
3. Vega-Hernandez G, Wojcik R, Engel SS. Cost-effectiveness of semaglutide versus dulaglutide for the treatment of type 2 diabetes in the UK. Diabetes Obes Metab. 2020;22(S3):30-38. PubMed
4. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834-1844. PubMed
5. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130. PubMed
6. American Diabetes Association Professional Practice Committee. Standards of Care in Diabetes, 2024. Diabetes Care. 2024;47(Suppl 1). PubMed