Healthcare leaders can now use composite NNT CPEA to assess treatments more fully, particularly among cardiovascular diseases that claims 18 million lives yearly worldwide. Tools such as number needed to treat (NNT) and cost per event avoided (CPEA) help evaluate options like GLP-1 receptor agonists (GLP-1 RAs), however weaknesses persist. Primary endpoints often miss wider gains, so a recent piece by Toliver et al. (2026) examines SELECT and REWIND trials, showing how composite NNT CPEA highlights economic and clinical value for semaglutide and dulaglutide.
CVD is linked closely with obesity, type 2 diabetes, and kidney disease in CKM syndrome, which cost billions annually, globally. GLP-1 RAs manage blood glucose, aid weight loss, and cut CVD risks, with semaglutide (2.4 mg weekly) succeeding in SELECT for overweight patients with CVD but without diabetes, and dulaglutide (1.5 mg weekly) working in REWIND for diabetes patients with CVD. Both reduced MACE-3—cardiovascular death, non-fatal heart attack, or stroke—although secondary outcomes like heart failure hospitalisations matter too. Standard NNT uses 1/absolute risk reduction from main endpoints only, which limits insight, whereas composite NNT CPEA includes more events for a complete picture.
Results from Composite NNT CPEA Calculations
Toliver et al. built three composites—MACE-3, MACE-5 (adds heart failure and unstable angina hospitalisations), and CKM (adds death from any cause, revascularisation, diabetes prevention, kidney events)—calculating NNT as 1/ARR, while CPEA multiplies NNT by follow-up time and US net prices (£9,500–£11,000 yearly after rebates), with SELECT averaging 34.2 months and REWIND 64.8 months.
| Endpoint | Semaglutide NNT | Semaglutide CPEA (£) | Dulaglutide NNT | Dulaglutide CPEA (£) |
|---|---|---|---|---|
| MACE-3 | 67 | 1,320,000 | 72 | 1,500,000 |
| MACE-5 | 49 | 980,000 | 64 | 1,330,000 |
| CKM | 8 | 151,000 | 23 | 483,000 |
Table from Toliver et al. (2026), converted to £ at 0.8 USD/GBP. CPEA drops sharply with broader endpoints.
As composites expand, NNT falls, with semaglutide reaching 8 for CKM and dulaglutide 23, while CPEA plunges 89% for semaglutide and 74% for dulaglutide; therefore, therapies prevent more events at lower cost when viewed holistically.
Implications for Health Economics and Market Access
Composite NNT CPEA shifts payer views, as primary CPEA tops £1.3 million per event—which is steep for budgets—while CKM views make therapies affordable. In the UK, NICE weighs QALYs and this metric aids rapid assessments, and clinicians see clearer benefits beyond MACE.
- Payers: Integrate composites in submission guidelines with CEA and budget impact models.
- Firms: Test CKM endpoints in trials; report net costs.
- Policymakers: Set standards for fair pricing via composites.
- Providers: Use in patient talks for informed choices.
Combine composites with full analyses, as they suit quick decisions.
Limitations and Future Directions
Trial populations differed slightly, so direct drug comparisons need caution. Real-world data will test transferability, and more trials should apply this method.
Composite NNT CPEA captures full therapy benefits in CVD and CKM, with semaglutide and dulaglutide shining under this lens—as CPEA drops as low as £151,000—so senior leaders benefit from this balanced tool, which they should adopt alongside CEAs to drive efficient systems.
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