2024 Top Story in Eye Care: Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression

The story that I would like to highlight for 2024 is the article that discussed the impact of glucagon-like peptide-1 (GLP-1) agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors on diabetic retinopathy progression.¹ I chose this story because diabetic retinopathy is the leading cause of blindness in the working population.² Recently, the FDA has approved hypoglycemic drugs such as GLP-1 agonists and SGLT2 inhibitors for the management of diabetes mellitus. These drugs are popular treatment options for diabetes owing to their additional beneficial effects on the cardiovascular, cerebrovascular, and renal systems. In addition, some of the GLP-1 agonists have been approved by the FDA for the treatment of obesity. Therefore, it is important to understand the effects of these drugs on diabetic retinopathy.

This article published by Wai and colleagues compared the effects of GLP-1 agonists and SGLT2 inhibitors on diabetic retinopathy. They conducted a retrospective clinical cohort study using TriNetX, a federated electronic health record network of global healthcare organizations. They identified patients diagnosed with diabetes mellitus who received monotherapy with GLP-1 agonists or SGLT2 antagonists from January 1, 2003, to November 9, 2023. For each medication group, 6481 matched patients were identified. The primary analysis involved patients with preexisting treatment-naïve type 1 and type 2 nonproliferative diabetic retinopathy (NPDR). The second group consisted of all patients with diabetes with or without retinopathy. The third group included patients with severe NPDR. The outcome measures were assessed at 3 months, 6 months, 1 year, and 3 years after the hypoglycemic medications were started. The main outcomes measured were progression to proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) development. Secondary outcomes included the need for ophthalmic procedures such as intravitreal injection, laser photocoagulation, and pars plana vitrectomy.

The patients in the GLP-1 group were more likely to develop DME and PDR. The GLP-1 group started off with a higher hemoglobin A1c (HbA1c) level and BMI. However, during the study, the HbA1c level was lower or not significantly different in the GLP-1 group compared with the SGLT2 group. Patients in the GLP-1 group who had NPDR at the start of the study were more likely to receive intravitreal anti-VEGF injections at 3 years. This was most likely because the patients receiving GLP-1 agonists were at a higher risk of developing DME and PDR.

The use of GLP-1 agonists has increased significantly in recent years. It is important for clinicians to recognize that these drugs may cause a worsening of diabetic retinopathy up to 3 years after starting treatment despite improved HbA1c levels. Patients with diabetes mellitus receiving GLP-1 agonists may need closer monitoring and more frequent intervention with intravitreal injections or lasers to prevent vision loss. The Diabetes Control and Complications Trial reported that improved blood glucose has been linked to an initial worsening of diabetic retinopathy; however, in the long term, retinopathy stabilizes.^3,4 It is surprising that DME and PDR continued to worsen up to 3 years after starting treatment. SGLT2 antagonists are effective at slowing diabetic nephropathy.⁵ In this study, the SGLT2 antagonists appeared to have a stronger protective effect on diabetic retinopathy. Both diabetic retinopathy and nephropathy are microvascular complications of diabetes mellitus. It has been previously shown that diabetic retinopathy is a predictor of diabetic nephropathy.⁶ Therefore, it is not surprising that SGLT2 inhibitors were less likely to cause the progression of diabetic retinopathy. Ophthalmologists must take a careful medication history, paying close attention to the type of hypoglycemic medications that our patients are using as these drugs may affect response to treatment despite good blood sugar control.