Neuropsychiatric Outcomes With Tirzepatide, Semaglutide, and Other GLP ‐1 Receptor Agonists
Authors' conclusion
In real-world practice, tirzepatide and semaglutide demonstrated comparable neuropsychiatric risk profiles over 2 years. Semaglutide was associated with lower psychiatric event rates compared with earlier-generation GLP-1 receptor agonists.
Study context
- Population
- Adults with T2D, obesity, or both initiating tirzepatide, semaglutide, or other GLP-1 RAs, July 2022–June 2025matched cohort
- Exposure
- Tirzepatide vs semaglutide; semaglutide vs other GLP-1 RAs
- Tirzepatiden = 85,546 pairs
- Other GLP-1 RAsn = 80,115 pairsreference
- Outcome
- Incident depression, anxiety, suicidal ideation and composite psychiatric outcome
- Follow-up
- Year 1 (day 31-365) and Year 2 landmark (day 366-730)
Methodological detailsnew-user design with 12-month washout, propensity-score matched, TriNetX Global Federated Network
- New-user design with 12-month washout
- Propensity-score matched
- TriNetX Global Federated Network
Main finding
As reported in the abstract
Composite psychiatric outcome, tirzepatide vs semaglutide
Tirzepatide vs SemaglutideHazard ratio (95% CI)
Year 1
0.984(0.950–1.019)
Year 2
1.002(0.960–1.046)
Observational data: associations, not effects.
Further findings
| Outcome | Estimate | |
|---|---|---|
| Anxiety, tirzepatidevs semaglutide · Year 2 | HR 1.052 (CI 1.001–1.106) | |
| Psychiatric outcomes, semaglutide vs other GLP-1 RAs · Year 1Semaglutidevs Other GLP-1 RAs | HR (depression) 0.811 (CI 0.770–0.855) | |
| Psychiatric outcomes, semaglutide vs other GLP-1 RAs · Year 1Semaglutidevs Other GLP-1 RAs | HR (anxiety) 0.915 (CI 0.871–0.961) | |
| Psychiatric outcomes, semaglutide vs other GLP-1 RAs · Year 1Semaglutidevs Other GLP-1 RAs | HR (suicidal ideation) 0.488 (CI 0.339–0.702) | |
| Psychiatric outcomes, semaglutide vs other GLP-1 RAs · Year 1Semaglutidevs Other GLP-1 RAs | HR (composite psychiatric outcome) 0.866 (CI 0.832–0.901) | |
| 0.20.5125Ratio (log scale) |
- Anxiety, tirzepatide vs semaglutide: nominally higher; interpret cautiously given multiple comparisons
Original publication
Neuropsychiatric Outcomes With Tirzepatide, Semaglutide, and Other GLP ‐1 Receptor Agonists. Diabetes Obes Metab. Published 8 July 2026. doi:10.
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