New generation agents for glycemic control and diabetic retinopathy progression: what we need to know?

Abstract

Aims: To report on the current evidence of early worsening of diabetic retinopathy (EWDR) in patients treated with new-generation antidiabetic agents, with a focus on glucagon-like peptide-1 receptor agonists (GLP1-RA).

Methods: A comprehensive analysis of current literature was conducted, with a focus on studies evaluating the impact of glycemic control strategies and GLP1-RA on DR progression. References from landmark studies and recent trials were analyzed.

Results: Intensive glycemic control, while effective in reducing long-term microvascular complications including DR, has been associated with EWDR, particularly in cases with rapid HbA1c reductions. Emerging evidence links novel antidiabetic agents, including GLP1-RA, with increased risk of EWDR, though different studies have conflicting results. However, the risk of EWDR seems not to be directly linked to retinal toxicity from specific antidiabetic agents, but more likely to the rapid glycemic improvement. Risk factors for EWDR in these patients include higher baseline HbA1c, rapid and significant reductions in HbA1c levels during the first months of treatment, longer duration of diabetes, and more advanced stages of DR at baseline, while mild or moderate non-proliferative DR seem not be at higher risk of DR progression.

Conclusions: While new antidiabetic therapies offer significant benefits for diabetes management, clinicians must be cautious when implementing intensive glycemic control in patients at risk for EWDR. Individualized treatment plans and close monitoring are essential to mitigate risks and optimize outcomes for patients with DR.

Keywords: Early worsening of diabetic retinopathy; Glucagon-like peptide-1 receptor agonists; SUSTAIN-6 trial; Semaglutide.