Objective:
To evaluate the risk of ischemic optic neuropathy (ION) associated with the initiation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in adults with type 2 diabetes.
Approach:
- Study Design: A large observational analysis using the Merative MarketScan Commercial Claims and Encounters database to emulate a hypothetical randomized trial from January 2017 through December 2022.
- Cohorts: Included adults aged 18 to 65 years with type 2 diabetes who initiated GLP-1 RAs, SGLT2i, or DPP-4i, excluding those with prior use of these medications or ischemic optic neuropathy.
- Outcome Measurement: The primary outcome was incident ischemic optic neuropathy, serving as a proxy for nonarteritic anterior ischemic optic neuropathy (NAION).
- Data Analysis: Adjusted for over 80 baseline characteristics using inverse probability of treatment weighting.
Key Findings:
- At 18 months, the adjusted cumulative risk of ION was approximately 9 cases per 10,000 for GLP-1 RA initiators compared to 6 per 10,000 for SGLT2i initiators, with 81 ION events among GLP-1 RA initiators, 48 among SGLT2i initiators, and 33 among DPP-4i initiators.
- The risk difference was about 3 cases per 10,000 between GLP-1 RAs and SGLT2is, and about 4 cases per 10,000 when compared to DPP-4is.
- The majority of ION events among GLP-1 RA initiators occurred in patients older than 50 years and predominantly in men.
- The risk differences were smaller and not statistically significant when requiring more specific outcome definitions.
Interpretation:
The study suggests a potential association between GLP-1 RAs and increased risk of ION, but residual confounding factors related to diabetes duration and severity may influence these findings.
Limitations:
- The observational design limits the ability to control for unmeasured confounding factors.
- The rarity of ION events reduces the precision of secondary and subgroup analyses.
- The study population was limited to commercially insured adults aged 18 to 65 years.
Conclusion:
The findings should be interpreted cautiously, considering the potential residual confounding and the established benefits of GLP-1 RAs.
Sources:
This content is an AI-generated, fully rewritten summary based on a published scholarly article. It does not reproduce the original text and is not a substitute for the original publication. Readers are encouraged to consult the source for full context, data, and methodology.
