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Role of Newer Oral Diabetes Medications in Preventing Diabetic Retinopathy

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Several new anti-diabetic drugs have paved the way not only as a treatment for diabetes but also for preventing retinopathy.

Medically reviewed by

Dr. Ankush Dhaniram Gupta

Published At August 11, 2023
Reviewed AtMay 2, 2024

Introduction

Diabetes is a chronic metabolic condition with several ill effects on many body parts. The food is broken down into sugar, which is released into the bloodstream. Diabetes occurs when the blood sugar level rises because the body does not produce the required amount of insulin or is not able to use the insulin produced. Diabetic people can experience several health problems, and diabetic retinopathy is one such complication that could lead to vision loss.

What Is Diabetic Retinopathy?

Diabetic retinopathy is a complication of diabetes. An increased blood sugar level damages the retina's blood vessels - the light-sensitive tissue present at the back of the eyes. Initially, it may be asymptomatic, but with time, it could lead to blindness. The retinal blood vessels exude blood and other fluids. This leads to swelling of the retinal tissues, causing blurred vision, and if left untreated, it can lead to blindness. It can affect both eyes. Early detection and treatment can help prevent one from becoming blind.

How Do the New Diabetes Medications Help in Preventing Diabetic Retinopathy?

The management of diabetes helps prevent diabetic complications by controlling the glycemic index. The first pharmacotherapy for the treatment of diabetes was insulin. After this, several oral anti-diabetic agents were developed for treating type 2 diabetes. Sulfonylureas were discovered in 1940, such as Chlorpropamide, Tolbutamide, and Acetohexamide. Drugs like Metformin came into use in the 1920s. With time, many new anti-diabetic agents have come into the picture. Some of them include dipeptidyl peptidase 4 inhibitors (DPP4), incretins (glucagon-like peptide-1 receptor agonists), sodium-glucose cotransporter-2 inhibitors (SGLT-2), thiazolidinediones and alpha-glucosidase inhibitors. These can be used independently or in combination with other drugs.

What Are the New Diabetes Medications That Prevent Diabetic Retinopathy?

The following are the newly discovered anti-diabetic medications that are useful in preventing or delaying the progression of diabetic retinopathy:

1. GLP-1 Agonists:

Glucagon-like peptide 1 agonists belong to the class of medications known as incretins. Incretins are a group of hormones that cause a reduction in blood glucose levels. They are released after eating and start the process of insulin secretion from the pancreas, thereby reducing the process of gastric emptying and decreasing appetite. As compared to the previous oral anti-hyperglycemic drugs, they lower the risk of hypoglycemia, cause less weight loss, and can be used weekly once.

Some studies have found complete regression and improved vision after a month of use of glucagon-like peptide 1 agonist. Whereas others have reported a deterioration in diabetic retinopathy with their usage. Individuals taking Semaglutide have been reported to have an adverse effect on diabetic retinopathy. However, according to a recent study, GLP-1 agonists were found to reduce the progression of diabetic nephropathy and have no effect on retinopathy. Semaglutide has been found to have a negative effect on the retina.

2. DPP4 Inhibitors:

DPP4 (dipeptidyl peptidase 4) is an enzyme that causes the degradation of GLP-1. DPP4-inhibitors delay the breakdown of incretins, thereby extending their mode of action. The DPP4-inhibitors are used orally and have fewer side effects than GLP-1 agonists. They have been found to have a protective effect on diabetic retinopathy. Sitagliptin prevents inflammation, cell death, nitrosative stress, and increased blood-brain barrier permeability in the retinal cells. Vildagliptin has been found to have an anti-hyperglycemic, anti-inflammatory, and anti-thrombogenic effect on the retina of fat rats. The DPP4-inhibitors may slow down the progression of diabetic retinopathy.

3. SGLT-2 Inhibitors:

SGLT-2 (sodium-glucose cotransporter-2) inhibitors are a group of anti-hyperglycemic drugs that cause reversible inhibition of SGLT-2 in the kidney tubules, leading to glucose excretion from the urine. It works by reducing one's weight without any risk of hypoglycemia. It has been found that Ipragliflozin, an SGLT-2 inhibitor that controls hyperglycemia slowed the progression of diabetic nephropathy, neuropathy, and retinopathy in rats. However, the study still needs to be carried out on humans.

4. Alpha-Glucosidase Inhibitors:

Alpha-glucosidase inhibitors like Acarbose impair the enzyme alpha-glucosidase to increase carbohydrate digestion time, thus decreasing glucose absorption. Acarbose significantly improves glycemic control, thus preventing the changes related to diabetes in the retina and eye lens. Acarbose prevents the thickening of the basement membrane in the retinal blood vessels, thereby decreasing the retinal blood flow rate and increasing glutathione levels.

5. Thiazolidinediones:

Thiazolidinediones are insulin sensitizers that enhance the action of insulin and increase its sensitivity in tissues. They also reduce hepatic gluconeogenesis and increase muscle and fat glucose uptake. Rosiglitazone reduces diabetes-induced cell death in retinal cells without inhibiting basement membrane thickening. It may also reduce the formation of small blood vessels in the retina.

6. Sulfonylureas:

Sulfonylureas are a group of medicines that stimulate the secretion of insulin. Hypoglycemia is a common side-effect of the drug. Not much data is available on the use of sulfonylureas on diabetic retinopathy. A study found that Gliclazide is more effective in preventing the progression of diabetic retinopathy than other sulfonylurea drugs.

7. Biguanides:

Biguanides such as Metformin have been shown to have cardioprotective effects in diabetic individuals. It is an anti-inflammatory and anti-angiogenic drug, this in turn prevents the progression of retinopathy. Metformin tends to protect the eyes from retinopathy.

Conclusion

Several new drugs are being researched for their use in diabetic retinopathy. With the rise of type 2 diabetes and complications like diabetic retinopathy, one must be aware of the new drugs and their effect on retinopathy. However, very few studies have been conducted to determine the efficacy of such drugs.

It is not easy to find out whether their effect on diabetic retinopathy is by improving glycemic control or by a direct impact of the drugs on the blood vessels of the retina. New drugs like DPP4-inhibitors, GLP-1 agonists, and SGLT-2 inhibitors have been used along with older drugs like Metformin because of their efficacy. The GLP-1 agonists are the only non-oral anti-diabetic drugs and can be administered weekly as subcutaneous injections.

Except for thiazolidinediones and Semaglutine, the other anti-diabetic drugs are effective in treating diabetic retinopathy. Cardiovascular studies have been made mandatory for all the new anti-hyperglycemic drugs. The relationship between the drugs and the development of diabetic retinopathy should also be included in such studies. Studies should be conducted to determine whether the benefits are independent of the impact of glycemic control.

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Dr. Ankush Dhaniram Gupta
Dr. Ankush Dhaniram Gupta

Diabetology

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