Risk of depression with GLP ‐1 receptor agonists use in overweight or obese adults with type 2 diabetes: A new‐user, active‐comparator cohort study
Authors' conclusion
GLP-1 RA initiation was associated with a statistically significant increase in depression risk compared to SGLT2i use (9% relative increase, 2.2% absolute risk difference over 1 year), particularly during the subacute period and in older adults. This observed association must be balanced against substantial mortality benefits. Enhanced monitoring and shared decision-making are warranted.
Study context
- Population
- Overweight/obese adults with newly diagnosed T2D, without prior mood disorders; deidentified electronic health record network, January 2016 to July 2024; mean age 56.8 years, 48.9% malepropensity score matched
- Participants
- 51,408 adults
- Exposure
- GLP-1 RA vs SGLT2i
- GLP-1 RAn = 25,704
- SGLT2in = 25,704reference
- Outcome
- Composite of:
- Incident depression diagnosis
- Antidepressant initiation
- Follow-up
- 1 month to 1 year post-initiation
Methodological detailsnew-user, active-comparator, 1:1 propensity score matching, electronic health record network
- New-user
- Active-comparator
- 1:1 propensity score matching
- Electronic health record network
Main finding
As reported in the abstract
Incident depression (diagnosis or antidepressant initiation) · 1 month to 1 year
Each group vs SGLT2iHazard ratio (95% CI)P value
GLP-1 RA
1.09(1.04–1.14)
P < 0.001- GLP-1 RA
- absolute risk difference 2.2%
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| All-cause mortality | 0.74 (0.63–0.88) | |
| 0.512Hazard ratio (log scale) |
| Outcome | HR |
|---|---|
| Incident depression, adults ≥65 yearsAssociation stronger in adults ≥65 years | 1.15 |
Original publication
Risk of depression with GLP ‐1 receptor agonists use in overweight or obese adults with type 2 diabetes: A new‐user, active‐comparator cohort study. Diabetes Obes Metab. Published 29 September 2025. doi:10.
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