Comparing the use of individual and composite terms to evaluate adverse drug event disproportionality: a focus on glucagon-like peptide-1 receptor agonists and diabetic retinopathy

ABSTRACT

Background: 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 events.

Research Design and Methods: Reports from the US Food and Drug Administration Adverse Event Reporting System were utilized to examine relationships between GLP-1RAs and diabetic retinopathy events. A disproportionality analysis was conducted using the proportional reporting ratio.

Results: Four GLP-1RAs demonstrated signals for diabetic retinopathy events. 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.

Conclusions: 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 suggest an association between four GLP-1RAs and diabetic retinopathy events.

KEYWORDS:

• Pharmacovigilance
• post-marketing surveillance
• adverse drug events
• glucagon-like peptide-1 receptor agonists
• proportional reporting ratio

Acknowledgments

We thank Holly Budlong, PharmD, PhD for her review of an earlier version of the manuscript.

Declaration of interest

JF Farley reports receiving personal fees from Takeda for expert witness testimony and grant support from Astra Zeneca to the University of Minnesota for an unrelated research project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author Contributions

DGD designed the study, conducted the statistical analysis, and drafted the manuscript. JFF contributed to the conception of the research project, interpretation of results, and review and editing of the manuscript. Both authors approved the final version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.