US Population Eligibility and Estimated Impact of Semaglutide Treatment on Obesity Prevalence and Cardiovascular Disease Events
Open accessAbstract
Background: Semaglutide 2.4 mg benefits weight loss and reduction of cardiovascular disease (CVD) risk factors in adults with obesity. We estimated the US population eligibility for semaglutide 2.4 mg (based on the weight management indication) and the impact on obesity and CVD events. Methods: We applied STEP 1 trial eligibility criteria to US adults aged ≥ 18 years in the US National Health and Nutrition Examination Survey (NHANES) 2015-2018 to estimate the US eligible population. Semaglutide weight changes in STEP 1 were applied to estimate the population impact on weight changes and obesity prevalence. We also estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. The difference in estimated risks with and without semaglutide “treatment” multiplied by the eligible NHANES weighted population represented the estimated “preventable” CVD events. Results: We identified 3999 US adults weighted to an estimated population size of 93.0 million [M] (38% of US adults) who fit STEP 1 eligibility criteria. Applying STEP 1 treatment effects on weight loss resulted in an estimated 69.1% (64.3 M) and 50.5% (47.0 M) showing ≥ 10% and ≥ 15% weight reductions, respectively, translating to a 46.1% (43.0 M) reduction in obesity (BMI ≥ 30 kg/m 2) prevalence. Among those without CVD, estimated 10-year CVD risks were 10.15% “before” and 8.34% “after” semaglutide “treatment” reflecting a 1.81% absolute (and 17.8% relative) risk reduction translating to 1.50 million preventable CVD events over 10 years. Conclusion: Semaglutide treatment in eligible US adults may substantially reduce obesity prevalence and CVD events, which may dramatically impact associated healthcare costs.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There has not been a head-to-head comparison for meaningful cardiovascular event rates between tirzepatide and semaglutide in a single trial in high-risk populations.
“Nevertheless, there has not been a head-to-head comparison for meaningful CV event rates between the two agents in a single trial in high-risk populations.13,14”
From Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: <i>post-hoc</i> analysis of the SURMOUNT-5 trial (2025) · cites this paper as [14]
The estimated baseline 10-year CVD risk in the SURMOUNT-5 data is slightly lower than in the work by Wong et al., due to the lower proportion of males and a younger population.
“The estimated baseline 10-year CVD risk in the SURMOUNT-5 data is slightly lower than in the work by Wong et al., due to the lower proportion of males (34% and 50%, respectively) and a younger population (mean age 44.8 and 47.3, respectively).”
From Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: <i>post-hoc</i> analysis of the SURMOUNT-5 trial (2025) · cites this paper as [14]
The association between tirzepatide versus semaglutide and CVD risk reduction is consistent with previous real-world evidence studies.
“The association between tirzepatide vs. semaglutide and CVD risk reduction is consistent with previous real-world evidence studies.13,20,21,14,40”
From Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: <i>post-hoc</i> analysis of the SURMOUNT-5 trial (2025) · cites this paper as [14]
The absolute 10-year CVD risk reduction is similar between this work and Wong et al. for both tirzepatide and semaglutide.
“While the absolute 10-year CVD risk reduction is similar between this work and Wong et al. for both tirzepatide and semaglutide, this work allowed the direct comparison of the two treatment groups in one single randomized and controlled study.”
From Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: <i>post-hoc</i> analysis of the SURMOUNT-5 trial (2025) · cites this paper as [14]
The results are consistent between these current analyses of SURMOUNT-5 data and those by Wong et al., particularly in the treatment effect of tirzepatide versus semaglutide on CVD risk reduction.
“The results are consistent between these current analyses of SURMOUNT-5 data and those by Wong et al.13,14 particularly in the treatment effect of tirzepatide vs. semaglutide on CVD risk reduction.”
From Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: <i>post-hoc</i> analysis of the SURMOUNT-5 trial (2025) · cites this paper as [14]
Cites
Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association
Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Anderson, C. A. M., Arora, P., Avery, C. L., Baker-Smith, C. M., Beaton, A. Z., Boehme, A. K., Buxton, A. E., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001123 · Cited by 8,300 · see citing works
Self-citationLiraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629 · see citing works
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1607141 · Cited by 6,900 · see citing works
Tirzepatide Once Weekly for the Treatment of Obesity
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206038 · Cited by 3,838 · see citing works
A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D. C. W., le Roux, C. W., Violante Ortiz, R., Jensen, C. B., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411892 · Cited by 2,724 · see citing works
Ryan, D. H., Lingvay, I., Colhoun, H. M., Deanfield, J., Emerson, S. S., Kahn, S. E., Kushner, R. F., Marso, S., Plutzky, J., Brown-Frandsen, K., et al. (2020) · American Heart Journal · doi:10.1016/j.ahj.2020.07.008 · Cited by 249 · see citing works
Jensterle, M., Rizzo, M., Haluzík, M., & Janež, A. (2022) · Advances in Therapy · doi:10.1007/s12325-022-02153-x · Cited by 215 · see citing works
Arnold, S. V., Inzucchi, S. E., Tang, F., McGuire, D. K., Mehta, S. N., Maddox, T. M., Goyal, A., Sperling, L. S., Einhorn, D., Wong, N. D., et al. (2017) · European Journal of Preventive Cardiology · doi:10.1177/2047487317729252 · Cited by 144 · see citing works
Self-citationLu, Y., Liu, Y., & Krumholz, H. M. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.025545 · Cited by 54 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Maddox, K. E. J., Elkind, M. S. V., Aparicio, H. J., Commodore-Mensah, Y. Y., de Ferranti, S. D., Dowd, W. N., Hernandez, A. F., Khavjou, O., Michos, E. D., Palaniappan, L. P., et al. (2024) · Circulation · doi:10.1161/cir.0000000000001256 · Cited by 397 · see citing works
“46 Our PRISM modeling exercise similarly suggested that reductions in obesity would translate into major improvements in cardiovascular events such as heart attacks and strokes, although they rely on assumptions about the relationship between obesity and event rates that predate these new therapies.”
GLP-1 agonists for obesity—A new recipe for success
Mozaffarian, D. (2024) · JAMA · doi:10.1001/jama.2024.2252 · Cited by 76 · see citing works
Mamas, M. A., Bays, H., Li, R., Upadhyay, N., Irani, T., Senyucel, C., Dunn, J. P., & Liu-Seifert, H. (2025) · European Heart Journal Open · doi:10.1093/ehjopen/oeaf117 · Cited by 24 · see citing works
“9,11 The results are consistent between these current analyses of SURMOUNT-5 data and those by Wong et al. 13,14 particularly in the treatment effect of tirzepatide vs. semaglutide on CVD risk reduction.”
Permeation enhancer-induced membrane defects assist the oral absorption of peptide drugs
Colston, K. J., Faivre, K. T., & Schneebeli, S. (2025) · Nature Communications · doi:10.1038/s41467-025-64891-0 · Cited by 22 · see citing works
Xu, Z., Ma, Z., Zhao, X., & Zhang, B. (2024) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-024-04950-0 · Cited by 19 · see citing works
Picoli, C. D. C., Tsibulnikov, S., Ho, M., Demambro, V. E., Feng, T., Eltahir, M., Le, P. T., Chlebek, C., Rosen, C. J., Ryzhov, S., et al. (2025) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00521.2024 · Cited by 13 · see citing works
“Thus, the development of GLP-1 receptor agonists (GLP-1RAs), such as semaglutide and liraglutide, has been gaining popularity in managing hyperglycemia and overweight/ obesity (13–19).”
Suicidality among users of glucagon‐like peptide‐1 receptor agonists: An emerging signal?
Lau, D., & Gamble, J. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15459 · Cited by 12 · see citing works
Nanna, M. G., Doan, Q. V., Fabricatore, A., Faurby, M., Henry, A. D., Houshmand‐Oeregaard, A., Levine, A., Navar, A. M., Scassellati Sforzolini, T., & Toliver, J. C. (2025) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.16370 · Cited by 10 · see citing works
“19 In this analysis, we aimed to estimate the potential population-level impact of semaglutide 2.4 mg in the United States.”
InfluentialCarris, N. W., Wallace, S., DuCoin, C. G., Mhaskar, R., Stern, M., & Bunnell, B. E. (2024) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2023-0464 · Cited by 9 · see citing works
Riehl-Tonn, V., Medak, K. D., Rampersad, C., Macphee, A., & Harrison, T. (2024) · Canadian Journal of Kidney Health and Disease · doi:10.1177/20543581241290317 · Cited by 8 · see citing works
“69 In the population-based research setting, Wong et al 83 applied the eligibility criteria from STEP-1 (ie, adults with obesity) and modeled semaglutide’s potential impact on obesity and CV events if used in eligible people from the United States.”
MethodYan, H., Karthikeyan, H., Fan, W., Yang, Q., & Wong, N. D. (2025) · JACC Advances · doi:10.1016/j.jacadv.2025.101773 · Cited by 4 · see citing works
Self-citationYang, B., Xu, J., Dao, X., Huang, Y., Liang, J.-L., Huang, J.-L., Gou, B., Yan, H., Chen, N., & Fan, J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104935 · Cited by 4 · see citing works
“Currently, the standard treatment involves the administration of lipid-lowering drugs, but no specific therapy exists for OCM [17].”
Shadbolt, C., Elkin, J., Schilling, C., Hua, X., Choong, P. F. M., & Dowsey, M. (2025) · Annals of Internal Medicine · doi:10.7326/annals-24-02878 · Cited by 4 · see citing works
Wong, N. D., Karthikeyan, H., & Fan, W. (2025) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-024-07583-z · Cited by 3 · see citing works
“…semaglutide 2.4 mg, identifying 93 million US adults with overweight or obesity to be eligible based on STEP 1 trial eligibility criteria, with up to a 1.8% absolute (17.8% relative) CVD risk reduction projected that translates to an estimated 1.5 million pre-ventable CVD events over 10 years [28].”
InfluentialSelf-citationHorn, D. B., Shukla, A. P., Huang, H., Twum, E. A., Allen, S. E., & Kiš, S. G. (2026) · Obesity Pillars · doi:10.1016/j.obpill.2026.100301 · Cited by 1 · see citing works
“Additionally, GLP-1 RA treatment has been associated with a reduction in CVD risk in adults with obesity [19].”
Dziewierz, A., & Siudak, Z. (2025) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-025-07789-9 · Cited by 2 · see citing works
“The conclusions are crucial since the potential target use of GLP-1 RA is huge and expectations for cardiovascular outcomes are promising [6, 7].”
Liu, S. (2025) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-025-07812-z · Cited by 1 · see citing works
“Accumulated evidence has already demonstrated that GLP-1 receptor agonists—exemplified by semaglutide [ 4] —hold considerable therapeutic promise in diabetes and cardiovascular disease [ 5].”
US eligibility and preventable cardiovascular disease events from semaglutide in type 2 diabetes
Karthikeyan, H., Fan, W., & Wong, N. D. (2025) · Diabetes & vascular disease research · doi:10.1177/14791641251376551 · Cited by 1 · see citing works
“…with the potential to prevent an estimated 1.5 million CVD events over 10 years re fl ecting a relative risk reduction of 18% compared to placebo, 13 which compared favorably to the actual 20% risk reduction observed in the SELECT trial examining the ef fi cacy of semaglutide 2.4 mg in reducing…”
InfluentialSelf-citationBabazadeh, D., Zhong, H.-M., & Steinberg, F. M. (2026) · Journal of NutriLife · doi:10.1016/j.tjnut.2026.101753
Chen, X., Tu, B., Li, Z., Gao, P., Xu, Y., & Yao, Y. (2026) · Frontiers in Bioscience · doi:10.31083/fbl49873
Characterizing Disparities in GLP-1 Receptor Agonist Use Among US Adults With and Without Diabetes
Elkin, J., Shadbolt, C., Schilling, C., Hii, M., Sumithran, P., Choong, P. F. M., & Dowsey, M. (2026) · Journal of general internal medicine · doi:10.1007/s11606-026-10506-3
Wong, N. D., Karthikeyan, H., Fan, W., & Electricwala, B. (2026) · JACC Advances · doi:10.1016/j.jacadv.2025.102517
Self-citationMidlife under pressure: the alarming rise of obesity and insulin resistance among US women.
Khoudary, S. E. E. (2025) · Menopause · doi:10.1097/gme.0000000000002702
Kubsad, S., Kishan, A., Gharpure, M., Saha, P., Bergstein, V. E., Ficke, J. R., & Aiyer, A. (2025) · Journal of the American Academy of Orthopaedic Surgeons · doi:10.5435/jaaos-d-24-01267
How ‘miracle’ weight-loss drugs will change the world
Reardon, S. (2024) · Nature · doi:10.1038/d41586-024-03589-7
- Authors
- Wong, N. D., Karthikeyan, H., & Fan, W.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Wong, Nathan D.
- Venue
- Cardiovascular Drugs and Therapy
- Published
- 2023-08-14
- Volume
- 39
- Issue
- 1
- Pages
- 75-84
- ISSN
- 0920-3206 (ISSN-L)
- 1573-7241
- PMC
- PMC11802588
- OpenAlex
- W4385798876
- Cited by
- 26
- References
- 19
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 8
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cardiovascular Drugs and Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- semaglutide, obesity, cardiovascular disease, weight loss, obesity prevalence, cardiovascular risk reduction, GLP-1 receptor agonists, NHANES, Framingham risk score, health care costs
- MeSH terms
- Heart Disease Risk Factors, Semaglutide, Adult, Aged, Cardiovascular Diseases, Eligibility Determination, Glucagon-Like Peptides, Female, Humans, Male, Middle Aged, Nutrition Surveys, Obesity, United States, Weight Loss, Prevalence, Treatment Outcome, Risk Assessment, Anti-Obesity Agents, Glucagon-Like Peptide 1, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
