Tirzepatide Safety Signals in FAERS

A 2026 review of multi-target medicines found post-marketing safety studies for 19 of 27 drugs introduced from 2022 through 2024 that remained on the European market. Tirzepatide had one of the largest evidence sets, with 16 pharmacovigilance studies listed by the reviewers. Their synthesis found lower reporting rates for some adverse events than with semaglutide, including acute kidney injury, and no significant tirzepatide suicidality signal in the cited reporting analyses.^[1]

The source is a review article that combines studies of medicines acting at more than one biological target, a concept called polypharmacology. The group ranges from cancer antibodies and kinase inhibitors to tirzepatide, which activates both GIP and GLP-1 receptors. The paper also catalogued 11 multi-target medicines among 38 EMA approvals in 2025, but tirzepatide belongs to the earlier post-marketing group rather than the 2025 additions.^[1]

What the review actually counted

The authors searched PubMed for safety evaluations of 27 multi-target drugs introduced from 2022 through 2024 and still sold in Europe. They found at least one post-approval study for 19. Most of those studies drew on the FDA Adverse Event Reporting System, or FAERS, a database of reports submitted by manufacturers, clinicians, patients and others. The review treats those records as early warning material, not as a count of how often an event occurs among everyone who uses a drug.^[1]

The review table listed 16 tirzepatide studies, including nine based on FAERS and one combining FAERS with the World Health Organization's VigiBase. The authors found repeated reports of gastrointestinal problems, administration errors and injection-site reactions, along with less established signals that still need confirmation. A separate 2024 FAERS analysis examined 20,409 tirzepatide reports and identified 116 adverse-event terms that met its statistical screening criteria. Thirty-eight percent concerned administration-site or procedural problems, while gastrointestinal events made up another substantial share.^[2]

That earlier analysis also found disproportionate reporting for nausea, pancreatitis, diabetic retinopathy and medullary thyroid cancer when tirzepatide was compared with all other drugs in FAERS. Yet its comparisons with the GLP-1 receptor agonist class were more mixed: tirzepatide had lower reporting odds for several gastrointestinal events, pancreatitis and diabetic retinopathy, but higher reporting for constipation and some other gastrointestinal terms.^[2] The result is a map of reporting patterns, not a verdict that the medicine caused each event.

The kidney comparison needs caveats

The review's most specific comparison concerned acute kidney injury. A 2025 analysis counted 92,807 US FAERS reports naming tirzepatide as the primary suspect drug, including 432 acute kidney injury reports. It counted 41,065 semaglutide reports, including 440 acute kidney injury reports. Acute kidney injury therefore appeared in 0.47% of the tirzepatide report set and 1.07% of the semaglutide report set. The reporting odds ratio for tirzepatide versus semaglutide was 0.44, with a 95% confidence interval from 0.38 to 0.50.^[3]

Those percentages are proportions within submitted reports. They are not incidence rates among people taking either medicine. FAERS has no reliable denominator for total exposed patients, reports may be duplicated or incomplete, and publicity can change which events get submitted. Semaglutide also had a longer and broader market presence during the period studied. The authors themselves state that the lower tirzepatide signal does not mean there is no kidney risk.^[3]

The database showed less disproportionate kidney-injury reporting for tirzepatide during that window. It did not randomly assign patients, measure kidney events against verified prescription counts or control fully for differences between the people receiving each drug. Our tirzepatide safety overview and semaglutide safety overview keep established clinical evidence separate from spontaneous-report signals.

The suicidality finding needs restraint

The review also reported no significant suicidality signal for tirzepatide relative to the signal seen with semaglutide in one 2025 FAERS study. That study analysed reports from 2004 through 2024 and found significant disproportionality for semaglutide in depression and suicide or self-injury categories. It did not find the same statistical signals for tirzepatide.^[4]

A missing signal cannot establish that an event never occurs, and a positive signal cannot establish that a drug caused it. Psychiatric history, the reason for treatment, differences in exposure time and stimulated reporting can all affect the comparison. The study abstract goes further by suggesting that tirzepatide may be a better choice for some patients, but its spontaneous-report design cannot support an individual treatment recommendation. That decision belongs with a qualified clinician who can assess the person's history and current symptoms.^[4]

What this review cannot settle

The 2026 review is useful because it gathers a scattered post-marketing literature and shows where signals recur. It also states the main weaknesses plainly: underreporting, reporting bias, inconsistent sex and age analysis, variable report quality and no denominator for calculating incidence. Those limits prevent causal claims and make direct rankings between medicines uncertain.^[1]

The comparison also does not erase known adverse events or replace trial and label evidence. The 2024 tirzepatide analysis found familiar gastrointestinal reporting and several signals that deserve continued study, while stressing that only the first 16 months of US market experience were available. Its three medullary thyroid cancer reports were too few to define a risk, and much of the age and sex information was missing.^[2]

Current reporting studies do not show tirzepatide performing worse than semaglutide on the kidney and suicidality comparisons highlighted by the review, but the data cannot prove lower clinical risk. Longer follow-up, validated exposure counts and studies designed around specific outcomes are needed. Regulatory status and approved uses remain separate questions, covered in the tirzepatide regulation overview.

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