Glucagon-like peptide-1 receptor agonists are not associated with retinal adverse events in the FDA Adverse Event Reporting System

Abstract

Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used for the treatment of type 2 diabetes. In large trials, the GLP-1RAs liraglutide and semaglutide improved cardiovascular outcomes, but semaglutide was associated with an increased risk of retinopathy progression. We herein evaluated the association between GLP-1RA and retinal adverse events (AE) in the Food and Drug Administration Adverse Event Reporting System (FAERS).

Research design and methods: We mined the FAERS between 2004q1 and 2017q1 (for a total of 9 217 555 AE reports) to analyze disproportionality and evaluate the association between GLP-1RAs and AEs involving the retina. We compared the frequency of retinal AEs among reports including GLP-1RAs and in those including other glucose-lowering medications (GLMs) as suspect or concomitant drugs.

Results: We retrieved 114 814 reports involving GLP-1RA and 694 725 reports involving other GLMs as suspect or concomitant drugs. The cumulative frequency of retinal AEs was 2.53/1000 for reports involving GLP-1RA vs 6.62/1000 for reports involving other GLMs, with a proportional reporting ratio of 0.38 (95% CI 0.34 to 0.43; P<0.0001). Reports involving GLP-1RAs listed significantly more comorbid conditions and concomitant medications. Findings were consistent after filtering the diabetes indication irrespective of concomitant GLM, in reports including and in those not including insulin, and for the various GLP-1RAs.

Conclusions: In the FAERS there is no evidence that GLP-1RAs are associated with AEs suggestive of retinopathy progression. Despite more comorbid conditions and concomitant medications, in reports with GLP-1RA the frequency of retinal AEs was significantly lower than in reports with other GLMs.

Keywords: adverse drug reactions; glp-1; pharmacoepidemiology; retinopathy.

Figure 1

Study flow chart. Sequential queries of the FAERS, including subanalyses, are represented with the respective number of total reports. FAERS, Food and Drug Administration Adverse Event Reporting System; GLMs, glucose-lowering medications; GLP-1RA, glucagon-like peptide-1 receptor agonists.

Figure 2

Disproportionality analysis for specific retinal adverse events. The proportional reporting ratios (PRR) are reported along with their 95% CI in model 1. *Significant after Bonferroni correction.

Figure 3

Comorbid conditions and concomitant medications. (A) Numbers of concomitant medications that were significantly more frequent or less frequent in reports with GLP-1RA or in reports with other GLMs. (B) Numbers of comorbid conditions (retrieved as indications for medications) that were significantly more frequent or less frequent in reports with GLP-1RA or in reports with other GLMs. GLMs, glucose-lowering medications; GLP-1RA, glucagon-like peptide-1 receptor agonists.

Figure 4

Results of sensitivity analyses. (A) The pooled PRRs for retinal AEs associated with GLP-1RAs resulting from sensitivity analysis (1), where reports were filtered by the diabetes indication irrespective of GLM, are compared with those of model 1 and model 2. (B) Pooled PRRs for retinal AEs associated with GLP-1RAs from sensitivity analysis (2), where reports including and those not including insulin are distinguished. (C) Pooled PRRs for retinal AEs associated with GLP-1RAs from sensitivity analysis (3), where exenatide, liraglutide, and other GLP-1RAs (albiglutide, dulaglutide, lixisenatide, and teduglutide) are examined separately. AE, adverse event; GLM, glucose-lowering medications; GLP-1RA, glucagon-like peptide-1 receptor agonists; PRR, proportional reporting ratio.