Glucagon-like peptide-1 receptor (GLP-1) agonists and sodium-glucose cotransporter-2 (SLGT-2) inhibitors are newer classes of hypoglycemic agents that were developed to assist with blood sugar control in patients with diabetes mellitus. While these drugs appear to have good ability to manage blood sugar levels, reducing long-term risks of microvascular problems, this retrospective investigation found that the use of GLP-1 agonists may be associated with increased risk of vision-threatening complications.
Study Design
Using data from the TriNetX dataset, this retrospective clinical cohort study assessed the impact of GLP-1 agonists and SGLT-2 inhibitors on progression to proliferative diabetic retinopathy (PDR) or the development of diabetic macular edema (DME) among 6481 patients with nonproliferative diabetic retinopathy undergoing monotherapy with either of these 2 drug classes. Patients were matched based on age, gender, ethnicity, race, baseline hemoglobin A1c (HbA1c), baseline body mass index (BMI), presence of type I or type II diabetes, and diabetic retinopathy severity status.
Outcomes
There was a higher rate of progression to PDR in the GLP-1 agonist cohort at all time points but particularly at 1 year (relative risk [RR] 1.26) and 3 years (RR 1.28) compared to the SGLT-2 inhibitor cohort. The GLP-1 agonist cohort also had a higher rate of DME at 3 months (RR 1.13), 6 months (RR 1.22), 1 year (RR 1.24), and 3 years (RR 1.29) than the SGLT-2 inhibitor cohort.
Limitations
All dataset-based studies are limited by the quality of the data in the dataset.
Clinical Significance
This study highlights the importance of educating patients who are on these medications, especially GLP-1 agonists, about the potential for worsening diabetic retinopathy and the possible need for more frequent ophthalmic screening. However, the importance of blood sugar control for systemic health may outweigh the concerns over the possibility of diabetic retinopathy progression.
Financial Disclosures: Dr. Ajay Kuriyan discloses financial relationships with 4DMT, Adverum, Annexon, National Eye Institute, Novartis, Alcon Pharmaceuticals (Grant Support); Alimera Sciences, Allergan, Bausch + Lomb, EyePoint Pharmaceuticals (Consultant/Advisor); Iveric Bio, Optos (Lecture Fees/Speakers Bureau); Lumata Health, Recens Medical (Consultant/Advisor, Private Equity/Stock Holder); Spark Therapeutics (Consultant/Advisor, Lecture Fees/Speakers Bureau); Genentech (Consultant/Advisor, Lecture Fees/Speakers Bureau, Grant Support).