Evidence map›Paper›PMID 42489387›Full record

ArticleJACC. Advances2026

Cardiovascular and Cerebrovascular Outcomes Risk Reduction Associated With Semaglutide vs Tirzepatide: A Target Trial Emulation.

Ahmed Y Azzam, Muhammed Amir Essibayi, Pranjal Rai, Hamza A Salim, Mustafa S Alhasan, Mohammad Anindo, Anas Hashem, Adam A Dmytriw, David J Altschul, Vivek S Yedavalli and 4 more

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Article in JACC. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Ahmed Y AzzamDepartment of Neuroradiology, WVU Rockefeller Neuroscience Institute, West Virginia University, Morgantown, West Virginia, USA. Electronic address: ahmedyazzam@gmail.com.
Muhammed Amir EssibayiDepartment of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Pranjal RaiDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Hamza A SalimDepartment of Neuroradiology, MD Anderson Medical Center, Houston, Texas, USA.
Mustafa S AlhasanRadiology Division, King Khaled Eye Specialist Hospital & Research Center, Riyadh, Saudi Arabia; Consultant Teleradiologist, Teleradiology Solutions, Ardmore, Pennsylvania, USA.
Mohammad AnindoDepartment of Hospital Medicine, Hattiesburg Clinic, Hattiesburg, Mississippi, USA.
Anas HashemDepartment of Cardiology, Houston Methodist Hospital, Houston, Texas, USA.
Adam A DmytriwNeuroendovascular Program, Massachusetts General Hospital, Harvard University, Boston, Massachusetts, USA; Nuffield Department of Surgical Sciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom; Neurointerventional & Neuroanalytics Consortium (NAN-C), School of Medicine, Toronto Metropolitan University, Toronto, Ontario, Canada.
David J AltschulDepartment of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
Vivek S YedavalliThe Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, USA.
Fabricio FeltrinDivision of Radiology - Neuroradiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Sumit SinghDivision of Radiology - Neuroradiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
James MilburnThe University of Queensland Medical School, Ochsner Clinical School, New Orleans, Louisiana, USA; Department of Radiology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA.
Dhairya A LakhaniDepartment of Neuroradiology, WVU Rockefeller Neuroscience Institute, West Virginia University, Morgantown, West Virginia, USA; Department of Neuroscience, WVU Rockefeller Neuroscience Institute, West Virginia University, Morgantown, West Virginia, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlucagon-like peptide-1 receptor agonists demonstrate cardiovascular benefits; however, head-to-head comparisons between semaglutide and tirzepatide remain limited.

objectivesWhether treatment effects differ by diabetes status is still limited in the current literature evidence. We compared cardiovascular outcomes between these agents stratified by type 2 diabetes status using target trial emulation approach.

methodsWe conducted a target trial emulation study following TARGET framework of 217,920 adults initiating semaglutide or tirzepatide based on TriNetX Research Network Platform. Patients were stratified by diabetes status and matched 1:1 on baseline characteristics (type 2 diabetes: 48,507 pairs; nondiabetic: 60,453 pairs). Primary outcomes included atrial fibrillation, heart failure (HF), and acute myocardial infarction. Secondary outcomes included ischemic stroke/transient ischemic attack, hemorrhagic stroke, and peripheral artery disease. Follow-up extended to 3 years.

resultsTirzepatide was associated with a lower risk across all outcomes at 1 and 3 years. For HF at 1 year, risk ratios were 0.82 (95% CI: 0.78-0.86) in diabetic and 0.60 (0.55-0.65) in nondiabetic patients, with risk differences of 1.5% and 0.9%, respectively. Effect modification by diabetes status was significant for atrial fibrillation (P = 0.003), HF (P < 0.001), and acute myocardial infarction (P = 0.019) at 1 year. Risk reduction associations appeared to strengthen over the 3-year follow-up period.

conclusionsTirzepatide was associated with more favorable risk reduction compared with semaglutide across multiple outcomes, with effect heterogeneity by diabetes status suggesting differential treatment associations across these populations.

Indexed as

cardiovascular outcomescerebrovascular outcomessemaglutidetirzepatidetype 2 diabetes

Identifiers

PMID42489387
PMCPMC13400122

What Socratic holds

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.