SGLT2 Inhibitors Outclass GLP-1s, DPP4is in Lowering Retinopathy Risk

Credit: Mayo Clinic

Sodium-glucose co-transporter 2 (SGLT2) inhibitors could provide a beneficial effect on the likelihood of sight-threatening diabetic retinopathy (DR), according to new data presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting.¹

By comparison, other glucose-lowering therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) conferred a similar risk of sight-threatening retinopathy as Dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylurea.

“In conclusion, SGLT2 inhibitor use was associated with a lower risk of sight-threatening retinopathy compared to other classes of glucose-lowering medications,” said presenting investigator Andrew J. Barkmeier, MD, an associate professor of ophthalmology at Mayo Clinic.

Clinical guidelines from the American Diabetes Association (ADA) have evolved to include the increasing evidence base on the benefit of SGLT2 inhibitors and GLP-1 RA medications for T2D independent of glycemic control.² These beneficial effects have included weight loss and protection against cardiovascular and kidney events.

Determination of the benefit-risk profile of glucose-lowering medications regarding vision-threatening retinal complications has not been completely defined. As a result, Barkmeier and colleagues sought to evaluate whether the choice of a glucose-lowering agent for T2D affects the risk of sight-threatening retinal complication development.¹

The retrospective observational database study, approximating an idealized target trial, involved adults (≥21 years) enrollees in US commercial, Medicare Advantage, and Medicare fee-for-service plans with T2D and moderate cardiovascular disease (CVD) risk who had no history of advanced diabetic retinal complications. These patients also had no baseline history of advanced diabetic retinal complications, initiating treatment with GLP-1 RA, SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas.

Barkmeier and colleagues used inverse probability of treatment weighting to emulate randomization. Time to first treatment for sight-threatening retinopathy, defined as diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), was evaluated across treatment cohorts using inverse propensity score weighted Cox proportional hazards models.

Overall, 371,698 patients were enrolled in the analysis. Of the population, 42,265 initiated GLP-1 RA, 53,476 initiated SGLT2 inhibitors, 78,444 initiated DPP-4 inhibitors, and 197,513 initiated sulfonylurea agents.

SGLT2 inhibitor use was linked to a reduced risk of sight-threatening retinopathy requiring treatment compared with all other medication classes. This included GLP-1 RA therapy (hazard ratio [HR], 0.73; 95% CI, 0.55–0.97), DPP-4 inhibitors (HR, 0.79; 95% CI, 0.64–0.97), and sulfonylurea (HR, 0.61; 95% CI, 0.50–0.74).

Meanwhile, GLP-1 RA use was correlated with a similar risk of sight-threatening retinopathy as DPP-4 inhibitors (HR, 1.07; 95% CI, 0.85–1.35) and sulfonylurea (HR, 0.83; 95% CI, 0.67–1.03).

“Relative inter-class risks were similar at both shorter and longer terms of use,” Barkmeier added.

References

1. _{Barkmeier A. Risk for Sight-Threatening Diabetic Retinopathy With GLP-1 Receptor Agonists, SGLT2 Inhibitors, DPP-4 Inhibitors, and Sulfonylureas in Type 2 Diabetes. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}
2. _{Hirsh BJ, Hirsch JS, Hmoud H, et al. A system approach to improving guideline-directed therapy for cardio-renal-metabolic conditions: The "beyond diabetes" initiative. Am J Prev Cardiol. 2023;16:100608. Published 2023 Sep 26. doi:10.1016/j.ajpc.2023.100608}