Potential molecular mechanism of action of sodium-glucose co-transporter 2 inhibitors in the prevention and management of diabetic retinopathy

ABSTRACT

Introduction

Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of drugs for the treatment of type 2 diabetes mellitus (T2DM), which have cardio-renal protective activity. Some studies have also found that this drug may have an eye-protective effect, especially in preventing diabetic retinopathy (DR).

Areas covered

A search was conducted on PubMed and Google Scholar for all articles published from January 2007 to May 2022. This paper provides a new insight into how new emerging diabetic therapy may be beneficial in the case of DR. SGLT2 inhibitors have been proven to delay DR progression. However, the drug mechanism in the pathophysiology of diabetic retinopathy has not yet been established.

Expert opinion

In clinical practice, using SGLT2 inhibitors is beneficial as it offers multiple advantages. They can control blood sugar levels while simultaneously suppressing the progression of DR and DME. There is potential that the use of other expensive and prolonged therapeutic modalities may no longer be necessary, reducing the burden of treatment for patients.

KEYWORDS:

• Diabetic retinopathy
• sodium-glucose co-transporter 2 inhibitors
• pericyte damage
• mTOR pathway
• polyol pathway
• SIRT/AMPK pathway
• oxidative stress

Article highlights

• SGLT-2 inhibitors are one of the new alternative treatments reported to have a beneficial effect on preventing the progression of diabetic retinopathy.

• Inhibiting SGLT2 activity is believed to prevent pericyte swelling and loss, the initial process of diabetic retinopathy formation.

• SGLT2 inhibitors suppress mTOR activation, which predominates during the late proliferative stage of diabetic retinopathy due to retinal hypoxia.

• SGLT2 inhibitors block the specific receptor on the aldose reductase enzyme, which disrupts the polyol pathway and prevents the formation of diabetic retinopathy.

• SGLT2 inhibitors activate the SIRT1/AMPK pathway as low-energy sensors to suppress inflammation and minimize microvascular injury.

• SGLT2 inhibitors have an antioxidant role in diabetic eyes, thus reducing oxidative stress.

• Further research into the multiple possible molecular actions of SGLT2 inhibitors in the case of diabetic retinopathy should be conducted.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.