The SUSTAIN-6 trial showed significantly higher rates of retinopathy complications in the semaglutide group compared to placebo. Observational studies have not consistently corroborated this finding raising questions about the appropriateness of composite variables and whether the relationship exists across the entire drug class or is limited to individual glucagon-like peptide 1 agonists (GLP-1RAs). The study objective was to evaluate the difference between using individual and composite terms to assess associations between GLP-1RAs and diabetic retinopathy complications.
Reports from the US Food and Drug Administration Adverse Event Reporting System were utilized to examine relationships between GLP-1RAs and twelve Medical Dictionary for Regulatory Activities terms associated with diabetic retinopathy events. A disproportionality analysis was conducted using the proportional reporting ratio.
Dulaglutide, exenatide, liraglutide and semaglutide demonstrated signals for diabetic retinopathy events. Semaglutide had five diabetic retinopathy signals identified. The GLP-1RA drug class had four diabetic retinopathy signals. Only semaglutide had a signal for the composite diabetic retinopathy outcome. The GLP-1RA drug class and the composite diabetic retinopathy outcome did not meet the PRR signal thresholds.
This study suggests the use of drug class level and composite outcome variables may mask diabetic retinopathy signals in comparison to individual drug assessments. Our results support the SUSTAIN-6 trial findings and further suggest an association between four GLP-1RAs and diabetic retinopathy adverse events.