Novel Agents in the Management of Diabetes and Risk of Worsening Diabetic Retinopathy.

ABSTRACT

PURPOSE: Novel therapies for diabetes have potent effects on glycemic control, obesity and cardiovascular risk reduction but some, including the popular drug semaglutide, have also been implicated in worsening of diabetic retinopathy (DR). Given the ubiquity of these new agents, understanding the risks to vision is important. Here we review the data for several newly available agents in terms of systemic efficacy and retinal safety. METHODS: Literature review. RESULTS: Novel antihyperglycemic treatments include incretin mimetics and enhancers, sodium-glucose cotransporter inhibitors, long-acting insulins, and insulin delivery systems. All improve glycemic control and some have been shown to reduce major cardiovascular outcomes. In a pivotal trial, semaglutide was associated with ∼75% increased risk of DR worsening. The novel long-acting insulin icodec, formulated for once-weekly dosing, showed increased risk of DR worsening over a once-daily insulin. No other recent antihyperglycemic agent was associated with DR worsening, though following the semaglutide trials, nearly all studies excluded patients with pre-existing DR. Cases of DR worsening were rare in all instances. Dedicated safety studies for semaglutide in DR are currently underway. CONCLUSION: For most patients being considered for treatment with a novel anti-hyperglycemic agent, benefits on systemic metabolic and cardiovascular health are very likely to outweigh potential retinal harms. Although the true risks of the new agents on DR are unclear since their safety data come from secondary endpoints, the most vulnerable patients are those with pre-existing high-risk DR, poor baseline glycemic control and using insulin.