Will GLP-1 Analogues and SGLT-2 Inhibitors Become New Game Changers for Diabetic Retinopathy?

Abstract

Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus (DM), estimated to affect approximately one-third of the diabetic population, and the most common cause of preventable vision loss. The available treatment options focus on the late stages of this complication, while in the early stages there is no dedicated treatment besides optimizing blood pressure, lipid and glycemic control; DR is still lacking effective preventive methods. glucagon-like peptide 1 receptor agonists (GLP-1 Ras) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors have a proven effect in reducing risk factors of DR and numerous experimental and animal studies have strongly established its retinoprotective potential. Both drug groups have the evident potential to become a new therapeutic option for the prevention and treatment of diabetic retinopathy and there is an urgent need for further comprehensive clinical trials to verify whether these findings are translatable to humans.

Sodium–glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists treatment: variable observations of sequelae on diabetic retinopathy

“…The racial, ethnic and regional differences in the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) on cardiovascular and renal outcomes has been highlighted very clearly in the review by Kunutsor et al 1 Likewise, since diabetic retinopathy (DR) and nephropathy share pathophysiological mechanisms and there is a defined correlation between severity of DR and diabetic nephropathy, the reno-protective properties of SGLT2-Is and GLP-1RAs should be translatable to retinopathy. 2 Interestingly, after adjustment for all known risk factors that are found to be associated with DR and sight-threatening diabetic retinopathy (STDR), it was found that ethnicity is an independent risk factor for incident DR and STDR with higher risk among ethnic minorities and Africans having a 36% higher risk of developing STDR. 3 GLP-1RAs and SGLT2-Is have a proven effect in reducing risk factors of DR, improvement of glucose control, blood pressure and lipid profile as possible mechanisms to reduce the risk of developing DR and its further progression when introduced early in the treatment.…”

“…3 GLP-1RAs and SGLT2-Is have a proven effect in reducing risk factors of DR, improvement of glucose control, blood pressure and lipid profile as possible mechanisms to reduce the risk of developing DR and its further progression when introduced early in the treatment. 2 Diabetic patients are vulnerable to loss of vision, with chronic hyperglycaemia promoting inflammation, oedema and retinal pathological changes. Therefore, directing these pathways via SGLT2-Is could signify prospects to decrease progression of DR in high-risk patients, Further clinical trials investigating potential retino-protective effects of SGLT2-Is is warranted.…”

“…Similarly, the effects of GLP-1RA are not limited to glycaemia per se, since GLP-1 receptors are extensively distributed in other tissues, having also been identified in the human retina, and it has been proven that this expression is present only in ganglion cell layers of the healthy human eyes with no such presence in the retina of patients with DR. 2 It is therefore important to adopt a personalised approach to therapy, taking into account ethnic variations in the development of diabetic complications.…”

“…Likewise, since diabetic retinopathy (DR) and nephropathy share pathophysiological mechanisms and there is a defined correlation between severity of DR and diabetic nephropathy, the reno-protective properties of SGLT2-Is and GLP-1RAs should be translatable to retinopathy. 2…”

“…GLP-1RAs and SGLT2-Is have a proven effect in reducing risk factors of DR, improvement of glucose control, blood pressure and lipid profile as possible mechanisms to reduce the risk of developing DR and its further progression when introduced early in the treatment. 2…”