Semaglutide vs Tirzepatide in FAERS: 192,791 US Reports
A pharmacovigilance analysis published in Cureus on 25 July 2026 pulled every cardiac adverse event report for semaglutide and tirzepatide out of the FDA Adverse Event Reporting System between January 2022 and March 2026. That is 56,799 reports for semaglutide and 135,992 for tirzepatide, 192,791 in total.
Tirzepatide accounts for more than twice as many reports. Semaglutide carries almost all of the cardiac disproportionality.
A framing note. Both are approved medicines and this analysis concerns patients. Peptra Labs supplies tirzepatide as reference material for laboratory research only, semaglutide is not in our catalogue, and nothing here is guidance about human use or a claim that either compound causes harm.
What the semaglutide analysis did
The method is the same one we covered a few days ago on the European side, and it is worth restating because everything downstream depends on it.
A disproportionality analysis does not measure how often an event happens. It measures how often an event gets reported for one drug relative to another, inside the same database. The authors used each drug as the other’s comparator, computed reporting odds ratios and proportional reporting ratios, and counted a signal as positive only when the ROR exceeded 1.0 and the lower bound of its 95 percent confidence interval also exceeded 1.0.
Using the two drugs against each other, rather than against the whole database, is the sensible choice here. Both are prescribed for overlapping reasons, both are under the same public attention, and both attract reports for the same non-pharmacological reasons.
What came out
Semaglutide produced significant signals in eight of twelve cardiac categories.
| Category | Reporting odds ratio |
|---|---|
| All cardiac adverse events | 2.85, CI 2.68 to 3.04 |
| Congestive heart failure | 8.09 |
| Cardiac failure | 3.69 |
| Cardiac arrest | 3.42 |
| Atrial fibrillation | 3.37 |
| Fatal outcomes | 3.14 |
Tirzepatide generated higher raw counts for palpitations and tachycardia, but the authors report that adjusting for report volume left semaglutide’s disproportionality intact.
That volume point is the one worth holding onto. Tirzepatide has 2.4 times the raw reports, so a naive count would put it far ahead on almost everything. The disproportionality runs the other way, and the reason it runs the other way is exactly what the authors then address.
A word in the abstract that reads backwards
The paper’s abstract describes the cardiac reporting as “disproportionately favorable to semaglutide”, and a reader in a hurry will take that to mean the drug came out looking safer.
It means the opposite. In this phrasing, the disproportionality favours semaglutide in the sense of pointing at it: it is the drug accumulating the excess reports. The conclusion says so plainly, that semaglutide demonstrates robust, disproportionate cardiovascular adverse event signals relative to tirzepatide, particularly for structural events.
We flag it because it is a genuine trap. Anyone quoting the abstract without the conclusion will invert the finding, and in a field where headline numbers travel faster than papers, that matters.
The sentence that keeps the result honest
The authors do not stop at the signal. They write that these findings likely reflect underlying demographic and indication-based risk differences rather than direct toxicity.
That is a substantial qualification and it is theirs, not ours.
Semaglutide has been on the market longer, in older populations, with a larger share of patients carrying established cardiovascular disease and diabetes. Tirzepatide’s user base skews younger and more weight-focused. If the two populations differ in baseline cardiac risk, then a drug prescribed to sicker hearts will accumulate more cardiac reports without doing anything to those hearts at all.
A congestive heart failure ROR of 8.09 is a large number. It is also exactly the number you would expect if one drug is disproportionately given to people who already have heart failure.
The authors close by saying prospective head-to-head cardiovascular trials remain essential, which is the correct thing to say and a reminder of what this study is not.
Europe and the United States, same method, different organ
We reported six years of European reports from EudraVigilance three days ago, where the same disproportionality method produced eye disorder signals for semaglutide against liraglutide and dulaglutide, and a much shakier psychiatric signal.
Two databases on two continents, the same statistical instrument, and the same compound accumulating signals in both. That convergence is worth noting and it is not proof of anything causal, because the two analyses share the same weakness. Both measure reporting. Both are shaped by which drug is in the news, which patients receive it, and who files the form.
The pattern in this class has been consistent all month. In a matched cohort where liver outcomes came out level between the two compounds, the endpoint was coded diagnoses. In a cohort built on coded events rather than measured physiology, nausea and vomiting were counted as records, not observations. Nearly all of the real-world evidence accumulating for this class measures what somebody wrote down.
There is a study design that would settle the cardiac question, and it exists in adjacent form. A comparative effectiveness analysis published in Diabetes Care in May 2026 examined major adverse cardiovascular events for tirzepatide against dulaglutide or semaglutide in type 2 diabetes. Events, not reports.
What this means for the catalogue
Neither of the compounds in this analysis is sold by us for human use, and one of them is not in the catalogue at all, but the methodological lesson transfers directly.
Retatrutide has no FAERS profile worth analysing, because post-marketing reporting requires a market and the triple agonist is still investigational. Anyone reading that silence as a safety advantage has made the same mistake in reverse: an absence of reports is an absence of exposure, not an absence of events.
For laboratories, our European research buyer guide covers procurement and documentation, everything is supplied on a research use only basis, and our ranking of the most-studied research peptides tracks the published record rather than the reporting databases.
References
- Singla A, Kaur G, Singh G, et al. Comparative Cardiovascular Pharmacovigilance of Semaglutide and Tirzepatide: A Food and Drug Administration Adverse Event Reporting System (FAERS) Database Analysis (2022-2026). Cureus, 25 July 2026. doi 10.7759/cureus.113371
- Ammendolia I, Mondello C, Esposito E, et al. Psychiatric and eye disorders associated with use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Naunyn-Schmiedeberg’s Archives of Pharmacology, 22 August 2026
- Ostrominski JW, Ortega-Montiel J, Wexler DJ, et al. Comparative Effectiveness of Tirzepatide Versus Dulaglutide or Semaglutide on Major Cardiovascular Events in Type 2 Diabetes. Diabetes Care, 1 May 2026
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The products referenced on this site are supplied for laboratory research use only. They are not medicines and are not intended for human or veterinary use. This article summarises published research for informational purposes and is not medical advice. Statements about third-party studies belong to their authors.
