GLP-1 agonists may hasten progression of diabetic retinopathy

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a family of drugs used to treat type 2 diabetes mellitus (T2DM) and are now also being used for promoting weight loss.

The two studies presented at the 2023 annual meeting of the American Society of Retina Specialists revealed that using injectable GLP-1 receptor agonists appears to hasten the progression of diabetic macular oedema (DME) and diabetic retinopathy.

In patients with and without diabetes, GLP-1 agonists can promote considerable weight loss. Moreover, the finding that sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins improve renal and cardiovascular function in type 2 diabetes patients has accelerated the use of these agents for blood sugar control.

Ehsan Rahimy, MD, an adjunct clinical professor at Stanford University School of Medicine, Palo Alto, California, and colleagues and colleagues looked for the conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME using a repository of data from more than 13,500 people taking either of the two kinds of medication. Secondary outcomes included the need for intravitreal injections, pars plana vitrectomy (PPV), or panretinal photocoagulation (PRP).

5446 participants were included in each treatment group after propensity score matching for age, sex, race, ethnicity, and baseline A1c. The mean age of the participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Key findings include:

· Patients taking GLP-1 inhibitors had higher conversion rates to PDR than those taking gliflozins at three years (6% versus 4%).

· Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

· People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs roughly 6%, respectively, required intravitreal injections.

· Similar trends were noted for the need for PRP and PPV, he added, although the absolute numbers of patients were small.

In other research, Ishani Kapoor, Drexel University College of Medicine, Philadelphia, PA, USA, and colleagues conducted a meta-analysis of data collected in 93 RCTs of the seven currently available GLP-1 agonists. It found only albiglutide was associated with diabetic retinopathy to a statistically significant degree.

Albiglutide more than doubled the early-stage diabetic retinopathy risk compared with placebo (relative risk 2.18).

Other GLP-1 agonists evaluated in the meta-analysis were lixisenatide, liraglutide, exenatide, dulaglutide, tirzepatide, and semaglutide. The findings were presented at the meeting.

"Our meta-analysis shows that albiglutide is associated with an increased risk of early-stage DR compared to placebo and lowered risk of late-stage diabetic retinopathy compared to insulin," Dr. Kapoor and the team wrote.

"There is a need for further studies to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage," they concluded.

Reference:

Kapoor, I., Sarvepalli, S. M., D’Alessio, D., Grewal, D. S., & Hadziahmetovic, M. (2023). GLP-1 Receptor Agonists and Diabetic Retinopathy: A Meta-Analysis of Randomized Clinical Trials. Survey of Ophthalmology. https://doi.org/10.1016/j.survophthal.2023.07.002