GLP-1RA use linked to over 2x higher nonarteritic anterior ischaemic optic neuropathy risk in type 2 diabetes
Background
Nonarteritic anterior ischaemic optic neuropathy (NAION) is a leading cause of acute vision loss in older adults, often linked to vascular risk factors. Patients with Type 2 Diabetes (T2D) are at increased risk for microvascular complications, including ocular issues. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for T2D management due to their glucose-lowering and cardiovascular benefits. However, the specific ocular safety profile of GLP-1RAs, particularly regarding the risk of NAION, has remained unclear, necessitating investigation into this potential adverse event.
Study Design
This nationwide registry-based nested case-control study utilized Danish health registries from 1996-2023. Researchers identified 201,776 metformin-treated adults initiating second-line antihyperglycaemic therapy. Among these, 123 incident NAION cases were matched to 4920 controls by birth year and sex using incidence-density sampling. Conditional logistic regression estimated adjusted hazard rate ratios (HRs) for GLP-1RA exposure, considering recency (0-90 days current; 91-365 days recent) and cumulative duration. Adjustments included socio-economic factors, hypertension, hypercholesterolaemia, sleep apnoea, and diabetes duration.
Results
GLP-1RA use was observed in 63/123 cases (51.2%) and 1688/4920 controls (34.3%). Ever use of GLP-1RAs was associated with a significantly higher NAION rate compared to other second-line therapies, with an adjusted HR of 2.13 (95% CI: 1.43-3.18). Current GLP-1RA use (0-90 days) showed an elevated rate (HR 2.28, 95% CI: 1.49-3.48), while recent use (91-365 days) had an imprecise estimate (HR 1.69, 95% CI: 0.88-3.25). The association demonstrated time-dependency by cumulative duration: > No clear increase was seen within 0-½ years (HR 0.80, 95% CI: 0.32-2.05), but rates were highest at ½-1 year (HR 3.63, 95% CI: 2.06-6.40) and 1-1½ years (HR 3.52, 95% CI: 1.73-7.17). These findings remained consistent after HbA1c adjustment and in a new-user analysis, reinforcing the association between GLP-1RA use and increased NAION risk in type 2 diabetes.
Key Findings
- GLP-1RA ever use associated with 2.13x higher NAION rate (HR 2.13, 95% CI: 1.43-3.18).
- Current GLP-1RA use (0-90 days) associated with 2.28x higher NAION rate (HR 2.28, 95% CI: 1.49-3.48).
- NAION risk peaked at ½-1 year of GLP-1RA use (HR 3.63, 95% CI: 2.06-6.40).
- Elevated risk continued at 1-1½ years of use (HR 3.52, 95% CI: 1.73-7.17).
- No clear increase in NAION risk observed within the first 0-½ year of GLP-1RA use (HR 0.80).
Why It Matters
Clinicians should counsel patients on the potential risk of nonarteritic anterior ischaemic optic neuropathy (NAION) when initiating GLP-1RA therapy, particularly during the first 1.5 years of treatment. This study highlights a significant safety concern that warrants increased vigilance for visual symptoms in patients on GLP-1RAs for Type 2 Diabetes. While GLP-1RAs offer substantial benefits, this finding suggests a need for a more comprehensive risk-benefit assessment, especially in patients with pre-existing ocular risk factors. Further research is needed to elucidate the underlying mechanisms and identify specific patient populations at highest risk, potentially leading to updated prescribing guidelines or monitoring protocols.
glp-1ra
type-2-diabetes
naion
optic-neuropathy
ocular-safety
cohort-study