Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep 2;5(5):oeaf117.
doi: 10.1093/ehjopen/oeaf117. eCollection 2025 Sep.

Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial

Mamas A Mamas  1 , Harold Bays  2 , Runjia Li  3 , Navneet Upadhyay  3 , Tanya Irani  3 , Cagri Senyucel  3 , Julia P Dunn  3 , Hong Liu-Seifert  3
Affiliations

Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial

Mamas A Mamas et al. Eur Heart J Open. .

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.

Keywords: Cardiovascular disease; Semaglutide; Tirzepatide.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: M.A.M.: Professor Mamas’ institution has received research grants from Terumo, Boston Scientific, and Abbott vascular. Professor Mamas is on the speakers bureau for Amgen, Terumo, and Biosensors and has consulting agreements with Eli Lilly, Boehringer Ingelheim, and Novo Nordisk. H.B.: Dr Harold Bays’ research site institution has received research grants from 89Bio, Allergan, Alon Medtech/Epitomee, Aligos, Altimmune, Amgen, Anji Pharma, Abbvie, AstraZeneca, Bioage, Biohaven, Bionime, Boehringer Ingelheim, Carmot, Chorus/Bioage, Eli Lilly, Esperion, Evidera, Fractyl, GlaxoSmithKline, HighTide, Home Access, Horizon, Ionis, Kallyope, LG-Chem, Madrigal, Merck, Mineralys, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Satsuma, Selecta, Shionogi, Skye/Birdrock, TIMI, Veru, Viking, Vivus, Zomagen. H.B. has served as a consultant (e.g. executive/national committee member and/or protocol/drug development advisor) for 89Bio, Altimmune, Amgen, Boehringer Ingelheim, Eva Pharma, Kiniksa, HighTide, Lilly, Novo Nordisk, Regeneron, Rivus, Veru, Zomagen, ZyVersa. R.L., N.U., T.I., C.S., J.P.D., and H.L.-S. are current employees and shareholders of Eli Lilly and Company.

Figures

Figure 1
Figure 1
Percent change from baseline in cardiovascular risk (%), in tirzepatide vs. semaglutide. Data are least-square mean for per cent (%) change from baseline. Error bars indicate standard error. MTD, maximum tolerated dose; SEMA, semaglutide; TZP, tirzepatide.
Figure 2
Figure 2
Percent change from baseline (PCFB) in cardiovascular risk, % in tirzepatide vs. semaglutide, by baseline subgroup. BMI, body mass index; MTD, maximum tolerated dose; SEMA, semaglutide; TZP, tirzepatide.
Figure 3
Figure 3
Predicted 10-year cardiovascular risk and risk factors in tirzepatide vs. semaglutide from baseline to Week 72. Data are least-square mean for post-baseline 10-year cardiovascular disease risk, and observed mean for baseline 10-year cardiovascular disease risk, body mass index, systolic blood pressure, and the proportion of under treatment for hypertension (%). Error bars indicate standard error. MTD, maximum tolerated dose; SEMA, semaglutide; TZP, tirzepatide.
See this image and copyright information in PMC

References

    1. Khan SS, Ning H, Wilkins JT, Allen N, Carnethon M, Berry JD, Sweis RN, Lloyd-Jones DM. Association of body mass index with lifetime risk of cardiovascular disease and compression of morbidity. JAMA Cardiol 2018;3:280–287. - PMC - PubMed
    1. Koskinas KC, Van Craenenbroeck EM, Antoniades C, Blüher M, Gorter TM, Hanssen H, Marx N, McDonagh TA, Mingrone G, Rosengren A, Prescott EB, Aboyans V, Blomstrom-Lundqvist C, Nielsen JC, Donal E, Döhner W, Ferrini M, Halvorsen S, Hassager C, Huber K, James S, Leclercq C, Linde C, McEvoy JW, McMurray J, Mihaylova B, Mindham R, Petersen S, Piepoli M, Rakisheva A, Rosselló X, Szymański P, Uchmanowicz I, Vrints C, Windecker S, Witkowski A, Zeppenfeld K. Obesity and cardiovascular disease: an ESC clinical consensus statement. Eur Heart J 2024;45:4063–4098. - PubMed
    1. Bays HE, Taub PR, Epstein E, Michos ED, Ferraro RA, Bailey AL, Kelli HM, Ferdinand KC, Echols MR, Weintraub H, Bostrom J, Johnson HM, Hoppe KK, Shapiro MD, German CA, Virani SS, Hussain A, Ballantyne CM, Agha AM, Toth PP. Ten things to know about ten cardiovascular disease risk factors. Am J Prev Cardiol 2021;5:100149. - PMC - PubMed
    1. Bays HE. Adiposopathy. JACC 2011;57:2461–2473. - PubMed
    1. Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, Marczak L, Mokdad AH, Moradi-Lakeh M, Naghavi M, Salama JS, Vos T, Abate KH, Abbafati C, Ahmed MB, Al-Aly Z, Alkerwi A, Al-Raddadi R, Amare AT, Amberbir A, Amegah AK, Amini E, Amrock SM, Anjana RM, Ärnlöv J, Asayesh H, Banerjee A, Barac A, Baye E, Bennett DA, Beyene AS, Biadgilign S, Biryukov S, Bjertness E, Boneya DJ, Campos-Nonato I, Carrero JJ, Cecilio P, Cercy K, Ciobanu LG, Cornaby L, Damtew SA, Dandona L, Dandona R, Dharmaratne SD, Duncan BB, Eshrati B, Esteghamati A, Feigin VL, Fernandes JC, Fürst T, Gebrehiwot TT, Gold A, Gona PN, Goto A, Habtewold TD, Hadush KT, Hafezi-Nejad N, Hay SI, Horino M, Islami F, Kamal R, Kasaeian A, Katikireddi SV, Kengne AP, Kesavachandran CN, Khader YS, Khang Y-H, Khubchandani J, Kim D, Kim YJ, Kinfu Y, Kosen S, Ku T, Defo BK, Anil Kumar G, Larson HJ, Leinsalu M, Liang X, Lim SS, Liu P, Lopez AD, Lozano R, Majeed A, Malekzadeh R, Malta DC, Mazidi M, McAlinden C, McGarvey ST, Mengistu DT, Mensah GA, Mensink GBM, Mezgebe HB, Mirrakhimov EM, Mueller UO, Noubiap JJ, Obermeyer CM, Ogbo FA, Owolabi MO, Patton GC, Pourmalek F, Qorbani M, Rafay A, Rai RK, Ranabhat CL, Reinig N, Safiri S, Salomon JA, Sanabria JR, Santos IS, Sartorius B, Sawhney M, Schmidhuber J, Schutte AE, Schmidt MI, Sepanlou SG, Shamsizadeh M, Sheikhbahaei S, Shin M-J, Shiri R, Shiue I, Roba HS, Silva DAS, Silverberg JI, Singh JA, Stranges S, Swaminathan S, Tabarés-Seisdedos R, Tadese F, Tedla BA, Tegegne BS, Terkawi AS, Thakur JS, Tonelli M, Topor-Madry R, Tyrovolas S, Ukwaja KN, Uthman OA, Vaezghasemi M, Vasankari T, Vlassov VV, Vollset SE, Weiderpass E, Werdecker A, Wesana J, Westerman R, Yano Y, Yonemoto N, Yonga G, Zaidi Z, Zenebe ZM, Zipkin B, Murray CJL. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017;377:13–27. - PMC - PubMed

Associated data

LinkOut - more resources