Comparative safety of glucose‐lowering medications on depression in adults with type 2 diabetes
Authors' conclusion
Sustained use of GLP-1RA or DPP4i was associated with small, increased risks of incident depression compared with SGLT2i. GLP-1RA use was also associated with increased risk of depression compared to SU. Patients and clinicians may consider these risks along with other potential benefits and risks when initiating glucose-lowering medications.
Study context
- Population
- Adults with T2D, new users of one glucose-lowering medication with no evidence of depression and no prior comparator dispensing in the 2 years before initiation; EHR data 2014–2022 from six integrated health systems6 cohorts, N = 54,773 to 227,414
- Exposure
- GLP-1 RA vs SGLT2i vs DPP-4i vs sulfonylureas (SU)
- Outcome
- Incident depression diagnoses
- Follow-up
- 2.5 years after drug initiation
Methodological detailscomparative safety trials emulated, electronic health records, six integrated health systems, new-user design, targeted minimum loss-based estimation with super learning
- Comparative safety trials emulated
- Electronic health records
- Six integrated health systems
- New-user design
- Targeted minimum loss-based estimation with super learning
Main finding
As reported in the abstract
Incident depression (sustained use) · 2.5 years
RD (95% CI)
GLP-1RAvs SUincreased risk with GLP-1RA
1.8%(1.3%–2.4%)
SGLT2ivs DPP4idecreased risk with SGLT2i
−0.7%(−1.2% to −0.2%)
- GLP-1RA vs SGLT2i · increased risk with GLP-1RA
- cumulative RD 1.0% (95% CI 0.6%–1.4%)
Observational data: associations, not effects.
Original publication
Comparative safety of glucose‐lowering medications on depression in adults with type 2 diabetes. Diabetes Obes Metab. Published 2 January 2026. doi:10.
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