SGLT-2 inhibitor, effective for patients with kidney disease

Prof. Eun-sil Ko and Hyuk-sang Kwon release RWE results for 90,000 domestic patients

Lower risk of terminal renal failure than hypoglycemic drugs in diabetics

Active research in nephrology, expected as a treatment for chronic kidney disease

SGLT-2 inhibitors, developed as a treatment for diabetes, are further expanding their indications.

 

It has proven its protective effect beyond simple cardiovascular safety, and recently, data proving the benefit of kidney disease is accumulating.

 

In patients with type 2 diabetes, SGLT-2 inhibitors prevented the deterioration of renal function, and in recent large-scale clinical trials, it was also effective in patients with renal impairment regardless of diabetes.

 

This rationale is not limited to Randomized Controlled Trials (RCT).

 

Various RWE studies (CVD-REAL) conducted by AstraZeneca confirm the usefulness of SGLT-2 in the field.

 

In a recent large-scale RWE study conducted on Koreans, CVD-REAL 2, which included 340,000 Koreans, confirmed the cardiovascular benefits in type 2 diabetes patients.

 

However, this CVD-REAL 3 KOREA conducted a study exclusively for Koreans.

 

Also, it has proven effective in diabetic patients with kidney disease.

 

Dailypharm met with Professor Koh Eun-sil, Nephrology of Yeouido St.

 

Mary's Hospital and Professor Hyuk-Sang Kwon, Endocrinology, who participated in the CVD-REAL 3 KOREA study, and heard about the significance of this study and the prospects of SGLT-2 inhibitors.

 

Professor Koh was the first author and Professor Kwon was the corresponding author.

 

From the left, Professor Koh Eun-sil and Professor Hyuk-Sang Kwon

The CVD-REAL 3 KOREA study is an RWE study conducted to confirm whether the renal function protection effect of SGLT-2 inhibitors, which was confirmed in previous RCT studies, appears even in the real world containing confounding factors.

 

The study analyzed 90,000 patients with type 2 diabetes in Korea using a propensity score matching technique to analyze patients who started taking SGLT-2 inhibitors and those who started taking other hypoglycemic drugs at a one-to-one ratio of 45016 patients each.

 

It is characterized by the fact that it is the same method as CVD-REAL 3 previously conducted in countries around the world, and that it is only for Koreans.

 

In the SGLT-2 inhibitor group, Forxiga (Dapagliflozin) was the most common with 73.3%, followed by Jariance (Empagliflozin) 20.8%, and Suglat (Ipragliflozin) 6%.

 

As a result, patients taking SGLT-2 had a 53% lower risk of developing end-stage renal failure than those taking hypoglycemic drugs.

 

In particular, patients with glomerular filtration rate (eGFR) of 60-90 and patients with 60 or less showed greater benefits.

 

In this group, SGLT-2 inhibitors had a lower risk of developing end-stage renal failure than taking hypoglycemic drugs by 61%, with or without proteinuria.

 

In addition, taking SGLT-2 inhibitors reduced death from all causes by 18% compared to taking hypoglycemic drugs.

 

Prof.

 

Koh Eun-sil said, "The follow-up period is somewhat short, but this study clearly confirmed the kidney protection effect of SGLT-2 inhibitors." "We participated and the rate was only about 11%, and this time, even a study only observed by Koreans came out in the same way as the global study." Professor Koh expected that this study will play a major role in resolving questions about racial differences.

 

In addition, the RWE study was thought to be helpful in predicting the effect of drugs in actual clinical practice.

 

Corresponding author Professor Kwon Hyuk-Sang also said, "Most of the SGLT-2 inhibitor studies have an average percentage of Asian applicants of 10%, so even if the results are good, it is questionable whether it will be effective in domestic patients." In addition, he added, "This study is meaningful in that it has proven its effectiveness in 100% Korean patients." He then explained, "I think this renal protective effect is a series of effects of the entire SGLT-2 inhibitor rather than a specific drug." He added, "However, since the guidelines are based on evidence, the recommendations will be given priority to drugs that have demonstrated cardiovascular or kidney benefits and have demonstrated cardiovascular or renal benefits."

The DECLARE-TIMI58 study confirmed the benefits of kidney in diabetics, and the DAPA-CKD study proved its effectiveness as a treatment for chronic kidney disease with or without diabetes.

 

Currently, AstraZeneca is trying to acquire indications for treatment of chronic kidney disease based on the clinical results of DAPA-CKD.

 

The guidelines of international conferences are also rapidly reflecting the paradigm shift caused by SGLT-2 inhibitors.

 

Recently, Kidney Disease Improving Global Outcomes (KDIGO) recommended a combination therapy of metformin and an SGLT-2 inhibitor as the first-line treatment for chronic kidney disease patients with diabetes based on Forxiga's clinical trial.

 

Although there are possibilities in various areas, it is evaluated that more follow-up observations should be made to determine whether the benefits can be safely maintained in the long term.

 

Nevertheless, Professor Koh looked forward to SGLT-2 inhibitors because there is no suitable treatment for chronic kidney disease.

 

Prof.

 

Koh said clinical studies of drugs that were expected in the field of chronic kidney disease as well as heart failure failed.

 

It has emerged as a hot issue in renal medicine as studies related to SGLT-2 inhibitors are actively conducted.

 

Of course, more analysis through long-term observation is needed, but she said she expects a lot of good data to come out in the future.