Glucagon-like Peptide-1 Receptor Agonists and Risk for Ischemic Optic Neuropathy : A Target Trial Emulation
Authors' conclusion
Use of GLP-1RAs was associated with higher 18-month risk for ION than use of SGLT2is and DPP4is, although absolute risk remained very low. Observed differences may reflect residual confounding.
Study context
- Population
- Patients aged 18–65 years with T2D initiating a GLP-1 RA, SGLT2i or DPP-4i; large US commercial claims database (January 2017 to December 2022)
- Exposure
- GLP-1 RA vs SGLT2i and vs DPP-4i
- Outcome
- Incident ischemic optic neuropathy (ION) as a proxy for NAION
- Follow-up
- 18 months
Methodological detailsobservational cohort study, inverse probability of treatment weighting, adjusted for >80 covariates, commercial claims database, No diagnostic codes specifically for nonarteritic anterior ischemic optic neuropathy (NAION), Missing data on key clinical factors (e.g., BMI, T2D duration) may contribute to residual confounding
- Observational cohort study
- Inverse probability of treatment weighting
- Adjusted for >80 covariates
- Commercial claims database
- No diagnostic codes specifically for NAION
- Missing data on key clinical factors (e.g., BMI, T2D duration) may contribute to residual confounding
Main finding
As reported in the abstract
ION risk per 10 000 patients
GLP-1RA
8.5 per 10 000
SGLT2i
5.5 per 10 000
DPP4i
4.2 per 10 000
RD, per 10 000 (95% CI)
GLP-1RAvs SGLT2iNNH 3333
3.0(0.4–5.7)
GLP-1RAvs DPP4iNNH 2778
3.6(1.1–6.1)
Observational data: associations, not effects.
Further findings
Ischemic optic neuropathy (ION) events among GLP-1RA users by age and sex
- ION events in GLP-1RA users
- 81
- Events in persons older than 50 years
- 69 (85.2%)
- Events in men
- 57 (70.3%)
RD by diabetes medication use (vs SGLT2i and DPP4i, respectively)
- Metformin monotherapy users: RD vs SGLT2i and DPP4i (attenuated)
- 2.0 and 4.1
- Users of ≥2 diabetes medications: RD vs SGLT2i and DPP4i
- 5.7 and 4.0
RD by subgroup
- Risk differences (RDs) higher in men, patients aged ≥50 years, and those with CVD or ophthalmic conditions; minimal differences in women and those <50 years
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
Glucagon-like Peptide-1 Receptor Agonists and Risk for Ischemic Optic Neuropathy : A Target Trial Emulation. Ann Intern Med. Published 14 July 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →