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Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial
Mamas A. Mamas, Harold Edward Bays, Runjia Li, Navneet Upadhyay, Tanya Irani, Çağrı Şenyücel, Julia P. Dunn, Hong Liu‐Seifert. European Heart Journal Open, 2025-08-29
Topic: Brain proteins, microglia and lab models
Abstract Aims Approximately two-thirds of obesity-related mortality is attributable to cardiovascular disease (CVD). The aim of this analysis is to examine predicted CVD risk reduction following weight loss in persons with obesity for primary prevention between tirzepatide and semaglutide, and projected CVD events that could be potentially prevented in the USA. Methods and results SURMOUNT-5 was a Phase 3b, open-label, randomized trial conducted in participants with obesity and without Type-2 diabetes, comparing tirzepatide (10 or 15 mg) with semaglutide (1.7 or 2.4 mg) and administered via weekly subcutaneous injection. Predicted 10-year CVD risks were compared between treatments at baseline and up to 72 weeks post-treatment among participants without prior CVD. The impact of cardiovascular risk reduction was estimated as the projected preventable CVD events over 10 years for tirzepatide and semaglutide in the USA. The average predicted 10-year CVD risk score before treatment was 9.3%. Treatment with tirzepatide was associated with significantly greater reduction in predicted 10-year CVD risk compared with semaglutide (absolute reduction from baseline of 2.4% and 1.4%, respectively, P < 0.001). Translating risk reduction to the US population who met treatment eligibility criteria and without prior CVD (∼85 million), an estimated 2 million CVD events could be potentially prevented over 10 years after 72 weeks of tirzepatide treatment, vs. 1.15 million with semaglutide. Conclusion In SURMOUNT-5, treatment with tirzepatide was associated with greater predicted 10-year CVD risk reduction compared with semaglutide. This post hoc analysis suggests tirzepatide treatment may provide greater benefit in primary prevention of CVD than semaglutide in people with obesity and overweight. Registration ClinicalTrials.gov: NCT05822830
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mamas, M. A., Bays, H. E., Li, R., Upadhyay, N., Irani, T., Şenyücel, Ç., et al. (2025). Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial. European Heart Journal Open. https://doi.org/10.1093/ehjopen/oeaf117
Vancouver
Mamas MA, Bays HE, Li R, Upadhyay N, Irani T, Şenyücel Ç, et al. Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial. European Heart Journal Open. 2025. doi:10.1093/ehjopen/oeaf117. PMID: 40980721.
BibTeX
@article{mamas2025-40980721,
author = {Mamas, Mamas A. and Bays, Harold Edward and Li, Runjia and Upadhyay, Navneet and Irani, Tanya and Şenyücel, Çağrı and Dunn, Julia P. and Liu‐Seifert, Hong},
title = {{Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial}},
journal = {European Heart Journal Open},
year = {2025},
doi = {10.1093/ehjopen/oeaf117},
pmid = {40980721},
url = {https://doi.org/10.1093/ehjopen/oeaf117}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Methods and results SURMOUNT-5 was a Phase 3b, open-label, randomized trial conducted in participants with obesity and without Type-2 diabetes, comparing tirzepatide (10 or 15 mg) with semaglutide (1.7 or 2.4 mg) and administered via weekly subcutaneous injection.
- Treatment with tirzepatide was associated with significantly greater reduction in predicted 10-year CVD risk compared with semaglutide (absolute reduction from baseline of 2.4% and 1.4%, respectively, P < 0.001).
- Conclusion In SURMOUNT-5, treatment with tirzepatide was associated with greater predicted 10-year CVD risk reduction compared with semaglutide.
Why it matters
This post-hoc analysis of the SURMOUNT-5 trial is about obesity and predicted cardiovascular risk, not Alzheimer's disease. It found tirzepatide was associated with a greater reduction in predicted 10-year cardiovascular disease risk than semaglutide.
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Study details
- Study designrandomized controlled trial
- Effect sizeor 2.4; 9.3%; 2.4%
- Evidence strengthHigh
How this study scored 59/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (European Heart Journal Open) |
| Journal's citation record | 0 / 4 | European Heart Journal Open: journal h-index 31 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 3 / 7 | Cited 23 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 11.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Hong Liu‐Seifert: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Eli Lilly (United States): institution h-index 744 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40980721) |
| Free to read | 2 / 2 | Free to read |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1093/ehjopen/oeaf117
- PubMed: 40980721
- Original source →
- Free full text: European Heart Journal Open →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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