Sodium-glucose co-transporter 2 inhibitors and diabetic retinopathy: insights into preservation of sight and looking beyond

Abstract

Sodium-glucose co-transporter 2 Inhibitors (SGLT2i) were initially developed as therapeutic options for patients with type 2 diabetes mellitus (T2DM). Recently, randomized clinical trials have investigated their effects in cardiorenal protection through major adverse cardiovascular event reduction and reductions in diabetic nephropathy. While multiple mechanisms are proposed for this protection, microvascular protection is the primary component of their efficacy. While not primarily emphasized in clinical trials, evidence in other studies suggests that SGLT2i may confer retinoprotective effects via some of the same mechanisms in the aforementioned cardiorenal trials. Diabetic patients are susceptible to vision loss with chronic hyperglycemia promoting inflammation, edema, and retinal pathological changes. Targeting these pathways via SGLT2i may represent opportunities for providers to decrease retinopathy in high-risk T2DM patients, reduce disease progression, and lower drug burden in diabetic retinopathy patients. Further comprehensive clinical trials investigating these associations are needed to establish the potential retinoprotective effects of SGLT2i.

Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class

“…SGLT2 inhibitors are often used in patients with T2DM worldwide [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. SGLT2 inhibitors lead to amelioration of glycemic control by enhancing urinary glucose excretion.…”

“…The main characteristics of T2DM are insufficient β-cell function and insulin resistance [ 1 , 2 , 3 ]. Since sodium-glucose cotransporter 2 (SGLT2) contributes to most of renal glucose reabsorption, inhibition of SGLT2 is promising for T2DM [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. In this review article, we show that SGLT2 inhibitors have surprisingly many multifaceted effects beyond prediction like some emerging magical medicine.…”

The role of concomitant immunosuppressants in impeding the progression of diabetic retinopathy: A pilot study

“…In addition, anti-VEGF therapy does not always provide resolution of DME, most likely due to causal mechanisms being via pathways other than VEGF leading to DR.[ 22 ] Approximately one-quarter of eyes do not respond fully to currently used anti-VEGF. [ 23 ]…”

“…As a result of the hyperglycemia, the increased glucose intracellularly is converted to sorbitol in an excessive amount leading to osmotic effect and cell death. [ 22 ]…”

Commentary: Oral management of diabetic retinopathy

“…Unlike other anti-diabetic drugs, oral sodium-glucose co-transporter 2 inhibitors (SGLT2i) have a positive effect on cardiorenal functions as well as on vascular endothelium. This also holds promise for delaying the progression of DR.[ 12 ] Preliminary data suggests SGLT2i is associated with reduction in central retinal thickness in eyes with chronic DME. [ 13 ]…”