GLP-1 RAs Associated With Small ION Risk Increase - Summary - MDSpire
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GLP-1 RAs Associated With Small ION Risk Increase
In an observational US target trial emulation, glucagon-like peptide-1 receptor agonist initiation was associated with about 3 to 4 more ischemic optic neuropathy cases per 10,000 patients over 18 months than two comparator drug classes.
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.
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