Autoimmune Disease Risk With GLP-1RA, DPP-4i, and SGLT2i Treatment in Patients With Diabetes
- Design
- Retrospective cohort · 236838 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationType 2 diabetes; EHR-coded autoimmune outcomes.
- Could weight loss explain it?
- Unknown[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 4Hypothesis-generating EHR emulation.
- Assessment
- Version 4 · Checked against the source by AI · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In matched US electronic health records of people with type 2 diabetes, GLP-1 drug users and SGLT2 inhibitor users had similar autoimmune disease rates. Compared with DPP-4 inhibitor use, GLP-1 use was associated with higher rates of psoriasis, psoriatic arthritis and autoimmune thyroiditis, but lower rates of dermatomyositis, bullous pemphigoid and giant cell arteritis. Observational; these are associations, not proof of cause.
01Findings
What the study reported
- Drugs
- Class unspecified
- Comparator
- DPP-4 inhibitors; SGLT2 inhibitors
- Primary outcome
- 3-year incident autoimmune diseases (target-trial emulation, TriNetX)
- Effect
- DPP-4i vs GLP-1RA: psoriasis HR 0.79, psoriatic arthritis 0.65, thyroiditis 0.68 (lower with DPP-4i); dermatomyositis 2.18, bullous pemphigoid 1.78 (higher with DPP-4i); giant cell arteritis also higher with DPP-4i (named in the conclusions; no HR in the abstract); GLP-1RA vs SGLT2i no differences
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Diabetes status
- type 2 diabetes required
- Sample size
- 236838
Study quality details
- Study design
- Retrospective cohort
- Sample size
- 236838
- Randomization
- no
- Blinding
- not stated
- Comparator
- DPP-4 inhibitors; SGLT2 inhibitors
- Follow up duration
- not stated
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% confidence interval [CI] 0
- Risk of bias
- coded outcomes; DPP-4i comparisons may reflect known DPP-4i associations (bullous pemphigoid) rather than GLP-1 effects
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Not stated
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- Not available in metadata.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- GLP-1 receptor agonists alter the risk of autoimmune disease.Mixed
No difference GLP-1RA vs SGLT2i; DPP-4i lower psoriasis/thyroiditis but higher dermatomyositis than GLP-1RA.
04Source
The source, as retrieved
Abstract
[OBJECTIVE] Dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used for type 2 diabetes, yet their comparative immunologic safety is uncertain. To address this gap, we evaluated autoimmune disease incidence among patients treated with these agents. [METHODS] We conducted emulated target trials using electronic health record data from 152 health care organizations in the TriNetX network (2016-2023). Adults with type 2 diabetes initiating DPP-4i, GLP-1RA, or SGLT2i monotherapy and no prior autoimmune disease were included. Propensity score matching balanced demographics, comorbidities, laboratory data, and medications. Cohorts comprised 118,419 matched DPP-4i versus GLP-1RA pairs, 102,810 DPP-4i versus SGLT2i pairs, and 105,869 GLP-1RA versus SGLT2i pairs. Primary outcomes included three-year risks of incident autoimmune diseases such as psoriasis, rheumatoid arthritis, systemic sclerosis, dermatomyositis, and multiple sclerosis. [RESULTS] Compared with GLP-1RA, DPP-4i was associated with lower risk of psoriasis (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.85), psoriatic arthritis (HR 0.65, 95% CI 0.53-0.79), and autoimmune thyroiditis (HR 0.68, 95% CI 0.59-0.76), but higher risk of dermatomyositis (HR 2.18, 95% CI 1.24-3.53) and bullous pemphigoid (HR 1.78, 95% CI 1.24-2.46). [CONCLUSION] Compared with GLP-1RA, DPP-4i use decreased psoriasis and thyroiditis risk but increased dermatomyositis, bullous pemphigoid, and giant cell arteritis risk. No significant differences were observed between GLP-1RA and SGLT2i treatments. These findings provide novel safety signals and may inform antidiabetic drug selection while guiding future mechanistic and prospective research.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 42415363 first ingestion |