Comparative Renal Safety of Tirzepatide and Semaglutide: An FDA Adverse Event Reporting System (FAERS)-Disproportionality Study.
Gandhi. Ayush A; Bhatt. Nilay N; Parhizgar. Alireza A
Key Findings
- Acute kidney injury (AKI) was reported in 0.47% of tirzepatide cases vs 1.07% of semaglutide cases.
- The reporting odds ratio (ROR) of 0.44 indicates a lower frequency of AKI reports for tirzepatide compared to semaglutide.
- Both drugs showed low overall AKI rates, but the data are from voluntary reports and may be biased.
Practical Outcomes
- If you’re concerned about kidney health, tirzepatide might be the safer choice over semaglutide, though both appear low risk. Keep well‑hydrated and consider periodic kidney function checks when starting any GLP‑1‑based therapy. Remember this is observational data, so stay alert for new research that could confirm these findings.
Summary
A big US safety database looked at kidney injury reports for two popular diabetes drugs, tirzepatide and semaglutide. It found that kidney injury was reported about half as often with tirzepatide (0.47% of reports) compared to semaglutide (1.07%). The study can’t prove cause and effect, but it suggests tirzepatide may be gentler on the kidneys.
Abstract
<b>Background:</b> Acute kidney injury (AKI) remains a serious complication among individuals with type 2 diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed and often regarded as kidney-protective, yet post-marketing reports have linked them to AKI. Tirzepatide, a newer dual GIP/GLP-1 agonist, shows well-documented metabolic benefits, but its renal safety in real-world use is not well characterized. <b>Methods:</b> We conducted a disproportionality analysis of the U.S. FDA Adverse Event Reporting System (FAERS) from January 2022 to September 2025. Reporting odds ratios (RORs) and proportional reporting ratios (PRRs) were used to compare AKI reporting between tirzepatide and semaglutide. <b>Results:</b> Among 133,872 reports (92,807 tirzepatide; 41,065 semaglutide), AKI was listed in 432 (0.47%) and 440 (1.07%) cases, respectively. The ROR for tirzepatide versus semaglutide was 0.44 (95% CI, 0.38-0.50), suggesting a lower reporting frequency for AKI with tirzepatide. <b>Conclusions:</b> In this real-world pharmacovigilance analysis, semaglutide but not tirzepatide showed a disproportionality signal for AKI. While causality cannot be confirmed, clinicians should ensure hydration and renal monitoring when initiating GLP-1 RAs, particularly semaglutide. Semaglutide showed a higher AKI reporting rate than tirzepatide, though these findings should be interpreted cautiously given reporting bias and potential confounders. Both agents appear safe, with low AKI frequency in practice. Further studies should determine if differences reflect biological or reporting effects. These findings support the need for larger epidemiologic studies to define risk modifiers and optimize clinical safety strategies.
Study Information
pubmed
2025
2025-10-29T00:00:00.000Z
10.3390/jcm14217678
40