GLP-1R expression and dermatological diseases: a mendelian randomization and real-world study
- Design
- Mendelian randomization · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Population unclearUNKNOWN: the genetic-association and FAERS populations are not described in the abstract; no age, BMI or diabetes data are given.
- Could weight loss explain it?
- PossiblyA two-step mediation MR attributed part of the bullous pemphigoid association to immune-cell phenotypes (largest 35.7%); weight and glycaemic mediation was not examined and no weight or HbA1c data are reported.
Adjusted for: other - Study tier
- Study tier 3LOW: single Mendelian randomization study, capped at LOW, with a supplementary FAERS pharmacovigilance analysis that would be VERY_LOW on its own.
- Assessment
- Version 3 · Two independent AI reviews agreed · 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.
Using genetic variants that change GLP-1 receptor expression, this Mendelian randomization study linked higher expression to a lower risk of bullous pemphigoid (OR 0.47) but a higher risk of psoriasis (OR 1.19) and urticaria (OR 1.41). A check of the FDA adverse-event reporting database found a lower bullous pemphigoid reporting signal for GLP-1 drugs than for SGLT2 inhibitors. Gene expression is not the same as taking the drug, and these are associations, not proof of cause.
01Findings
What the study reported
- Drugs
- Glp-1 receptor agonists
- Dose
- various
- Comparator
- MR: genetically proxied higher versus lower GLP-1R expression (no drug comparator); FAERS: SGLT2 inhibitor reports
- Primary outcome
- risk of dermatological diseases (bullous pemphigoid, psoriasis, urticaria) by genetically proxied GLP-1R expression
- Effect
- Genetically proxied GLP-1R expression was linked to lower bullous pemphigoid risk (OR 0.47) and higher psoriasis (OR 1.19) and urticaria (OR 1.41) risk; FAERS GLP-1RA reports showed a lower bullous pemphigoid reporting signal than SGLT2 inhibitor reports
- 95% confidence interval
- 95% CI = 0.31-0.72 (bullous pemphigoid)
- P value
- P < 0.001
- Follow-up
- Not stated
- Adverse events
- Genetically higher GLP-1R expression was linked to higher risk of psoriasis (OR 1.19) and urticaria (OR 1.41); FAERS showed a lower bullous pemphigoid reporting signal for GLP-1RAs than for SGLT2 inhibitors
- Limitations
- The main exposure is genetically proxied GLP-1 receptor expression, not drug use, and the drug data come from a spontaneous-report database with no denominator; populations and sample sizes are not given in the abstract.
Who was studied
- Obesity status
- not reported in abstract
- Diabetes status
- not reported in abstract
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- not reported in abstract
Study quality details
- Study design
- Mendelian randomization
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- n/a
- Comparator
- MR: genetically proxied higher versus lower GLP-1R expression (no drug comparator); FAERS: SGLT2 inhibitor reports
- Follow up duration
- not stated
- Outcome type
- hard
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- UNKNOWN
- Statistical precision
- CI reported: 95% CI = 0.31-0.72 (bullous pemphigoid)
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- The authors declare no competing interests.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Although glucagon-like peptide-1 receptor (GLP-1R) is widely expressed in multiple tissues and organs including skin and subcutaneous tissue, with diverse physiological roles in metabolism and immunity, the potential causal association between GLP-1R expression and dermatological diseases remains unclear. [METHODS] Available cis-expression quantitative trait loci (cis-eQTLs) were selected as genetic instruments for GLP-1R expression. A two-sample Mendelian randomization (MR) analysis was employed to assess the potential causal association between GLP-1R expression and dermatological diseases. Subsequently, a two-step mediation MR analysis was conducted to explore the mediators between GLP-1R expression and dermatological diseases. Finally, a real-world pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) database was conducted to provide supplementary real-world evidence. [RESULTS] Our study revealed distinct associations between GLP-1R expression and dermatological diseases. Specifically, GLP-1R expression was significantly associated with a reduced risk of bullous pemphigoid (OR = 0.47, 95% CI = 0.31-0.72, P < 0.001), as well as an increased risk of psoriasis (OR = 1.19, 95% CI = 1.08-1.32, P < 0.001) and urticaria (OR = 1.41, 95% CI = 1.23-1.61, P < 0.001). Further mediation MR analysis suggested that the immune cell phenotype HLA-DR on B cells might mediate the causal association between GLP-1R expression and bullous pemphigoid, with an estimated mediation proportion of 35.7% (P = 0.003). Other immune cells including Monocytic Myeloid-Derived Suppressor Cells Absolute Count, HLA-DR on CD14 + CD16- monocytes, and HLA-DR on CD14 + monocytes were also identified as potential mediators, with estimated mediation proportions of 23.6% (P = 0.010), 13% (P = 0.024), and 12.7% (P = 0.036), respectively. In the complementary FAERS analysis, consistently, GLP-1RAs reports showed a lower reporting signal for bullous pemphigoid than sodium-glucose cotransporter 2 inhibitors (SGLT2is) reports. [CONCLUSION] Our findings suggest that GLP-1R expression is associated with a reduced risk of bullous pemphigoid, which may be partly mediated by specific immune cell phenotypes.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Oct 11, 2026 | 42842067 first ingestion |
| pubmed | Oct 11, 2026 | 42842067 duplicate matched on doi |
| pubmed | Oct 11, 2026 | 42842067 duplicate matched on doi |
| pubmed | Oct 18, 2026 | 42842067 duplicate matched on doi |
| pubmed | Oct 18, 2026 | 42842067 duplicate matched on doi |
| pubmed | Oct 18, 2026 | 42842067 duplicate matched on doi |