Aleksandra Rachitskaya, MD: Effect of GLP-1 Agonists on Diabetic Retinopathy

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Presented at AAO 2023, a retrospective study found no statistically significant difference in retinopathy worsening between GLP-1 RAs and SGLT2 inhibitors.

New research highlighted the need for increased research into the effects of glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment on the progression of diabetic retinopathy.

The data, presented at the 127th Annual American Academy of Ophthalmology (AAO) Meeting in San Francisco, California, showed no statistically significant difference in retinopathy worsening between treatment with GLP-1 RA and SGLT2 inhibitors. However, investigators suggested more data are needed to understand the early worsening of diabetic retinopathy with the use of the growing popularity class of diabetic medication.

“In terms of the results, what we found is that there was no association with either worsening by ICD-10 codes or any type of worsening and that was before and after propensity score matching,” said Aleksandra Rachitskaya, MD, an assistant professor of ophthalmology at Cole Eye Institute, Cleveland Clinic, in an interview with HCPLive. “One thing to note is that when we looked at hemoglobin A1c change in our population, at one year, it was not statistically significant, it was a very small improvement. That goes into consideration as we talk about what this data means."

Both the progression and development of diabetic retinopathy have been associated with several risk factors, consisting of diabetes disease duration, poor glycemic control, and poorly controlled hypertension. In advanced stages, diabetic retinopathy can lead to irreversible blindness.

GLP-1 RAs are a medication class typically used for treating type 2 diabetes (T2D) and obesity management. However, some literature has suggested an association between certain GLP-1 RA medications and the early worsening of the diabetic retinopathy phenomenon.

In the SUSTAIN-6 trial, semaglutide, a GLP-1 RA, showed higher rates of retinopathy complications, including vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation.

The label for semaglutide (OZEMPIC) included information from the SUSTAIN-6 trial. In the 2-year trial, among patients with T2D, and high cardiovascular risk, more events of diabetic retinopathy complications in patients treated with semaglutide (3.0%) compared to placebo. The absolute risk increase was also larger among those with a history of diabetic retinopathy at baseline (semaglutide, 8.2%; placebo, 5.2%) than those without a known history (semaglutide, 0.7%; placebo, 0.4%).

Rapid improvement in glucose control has been linked to temporary worsening of diabetic retinopathy, but the effect of semaglutide on diabetic retinopathy complications has not been studied. The investigative team retrospectively analyzed the real-world effect of the GLP-1 RA on DR progression, with patients treated with SGLT2 inhibitors being used as controls.

Diabetic retinopathy worsening was defined as ICD-10 code worsening and development of vitreous hemorrhage, or conditions requiring intravitreal injections or photocoagulation. Out of 692 patients treated with GLP-1 RA and 289 patients treated with SGLT2 inhibitors, there were no statistically significant differences in diabetic retinopathy worsening.

For more insight into the analysis, watch the full interview with Dr. Rachitskaya.

References

Rachitskaya A. The Effect of GLP-1 Receptor Agonists on Diabetic Retinopathy Progression. Presented at the 2023 American Academy of Ophthalmology Annual Meeting, November 3 – 6, 2023.

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