The Composite Number Needed to Treat for Semaglutide in Populations with Overweight or Obesity and Established Cardiovascular Disease Without Diabetes
Open accessAbstract
Number needed to treat (NNT), an outcome measure derived from the estimated risk results of clinical trials, is widely used to demonstrate value to stakeholders by identifying how many patients require treatment to avoid one event of interest. However, NNTs calculated for primary trial endpoints may underestimate a treatment’s value by not considering other outcomes. In this secondary analysis of data from the SELECT cardiovascular (CV) outcomes trial, we aimed to determine the NNT for semaglutide for major adverse cardiovascular events (MACE), in addition to NNTs when other clinically and payer-relevant outcomes are included. This study is a secondary analysis of data from the randomized, double-blind SELECT trial (ClinicalTrials.gov NCT03574597) of once-weekly subcutaneous administration of semaglutide compared with placebo in 17,604 patients with overweight or obesity and with established cardiovascular disease (CVD) (39.8 months mean follow-up). The outcomes were NNT 3P-MACE (based upon the trial’s composite primary endpoint of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke), NNT EXTENDED (inclusive of NNT 3P-MACE , hospitalization for any cause, coronary revascularization, and non-CV death), and NNT CKM (inclusive of NNT EXTENDED , glycated hemoglobin level [HbA 1c ] ≥ 6.5%, and a 5-point nephropathy composite). The relative risk reductions observed for the events comprising the NNTs were 20% (NNT 3P-MACE ), 20% (NNT EXTENDED ), and 41% (NNT CKM ). At 1 and 4 years post initiation of semaglutide, NNT 3P-MACE was 125 and 58, NNT EXTENDED was 49 and 25, and NNT CKM was 20 and 11, respectively. When clinically and payer-relevant outcomes from the SELECT trial are included in calculations of NNT, semaglutide was associated with greater risk reductions and lower estimates of NNT than for the primary endpoint alone. Our findings suggest that including the broader effects of semaglutide beyond the primary trial endpoint recognizes additional value to stakeholders.
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In the SELECT trial, GLP1-RAs were highly effective with sustained intervention, with a number needed to treat to prevent one cardiovascular event of 67 patients following a mean duration of treatment of 34.2 ± 13.7 months.
“In the SELECT trial, GLP1-RAs were highly effective with sustained intervention, with a number needed to treat (NNT) to prevent one cardiovascular event of 67 patients following a mean duration of treatment of 34.2 ± 13.7 months.”
From The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity (2025) · cites this paper as [90]
The Results table reports an NNT of 67 for SELECT’s primary cardiovascular composite endpoint with semaglutide, at 39.8 months’ mean follow-up. The cited paper does not report the claimed 34.2 ± 13.7 months of treatment, and its result concerns semaglutide rather than GLP-1 receptor agonists as a class. The indexed passages have no page numbers. (LLM, conf=0.89)
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Cited by
Sorted by citations
Scragg, J., Koutoukidis, D. A., Dirksen, C., Heitmann, B. L., & Jebb, S. A. (2025) · Med · doi:10.1016/j.medj.2025.100805 · Cited by 16 · see citing works
- Authors
- Lübker, C., Bhavsar, J., Duque do Vale, R., Emerson, S. S., Nørtoft, E., Plutzky, J., Roberts, G., Tarp, J. M., & Lincoff, A. M.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- University of Washington (US)
- Brigham and Women's Hospital (US)
- Health Economics and Outcomes Research (United Kingdom) (GB)
- Cleveland Clinic (US)
- Corresponding author
- Lübker, Christopher
- ORCID
- Venue
- Advances in Therapy
- Published
- 2025-03-29
- Volume
- 42
- Issue
- 5
- Pages
- 2513-2525
- ISSN
- 0741-238X (ISSN-L)
- 1865-8652
- PMC
- PMC12006245
- OpenAlex
- W4409039208
- Cited by
- 5
- References
- 9
- Citations by year
- 2026: 4 · 2025: 1
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Advances in Therapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- semaglutide, number needed to treat, major adverse cardiovascular events, obesity, overweight, established cardiovascular disease, SELECT trial, HbA1c, diabetic nephropathy, hospitalization, coronary revascularization, GLP-1 receptor agonists, treatment value
- MeSH terms
- Secondary Data Analysis, Semaglutide, Aged, Cardiovascular Diseases, Double-Blind Method, Glucagon-Like Peptides, Female, Humans, Male, Middle Aged, Obesity, Randomized Controlled Trials as Topic, Clinical Trials, Phase III as Topic, Overweight, Glucagon-Like Peptide 1, Numbers Needed To Treat
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