Evidence for Cardiorenal Protection with SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Patients with Diabetic Kidney Disease

Abstract

For almost two decades, the management of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) was based on the optimal glycemic and blood pressure control as well as on the adequate blockade of the renin-angiotensin-system. Over the past few years, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and glucagone-like peptide 1 receptor agonists (GLP1-RAs) were added to our therapeutic armarhatum, offering promise for more effective mitigation of the substantial residual cardiorenal risk of these patients. Large randomized controlled trials (RCTs) designed to demonstrate the cardiovascular safety of SGLT-2 inhibitors and GLP1-RAs showed that these novel anti-diabetic medications improve cardiovascular outcomes in patients with T2DM. RCTs conducted specifically in CKD patients with or without T2DM demonstrated that SGLT-2 inhibitors were also effective in retarding the progression of kidney injury to end-stage kidney disease. The kidney protective effects of GLP1-RA are not yet proven, but RCTs are currently ongoing to investigate this crucial research question. In this article, we review the available clinical-trial evidence supporting the use of SGLT-2 inhibitors and GLP1-RAs for cardiorenal protection in patients with T2DM and CKD. We provide clinical practice recommendations for a personalized approach in the use of these novel therapies, according to the severity of CKD and the presence of other cardiometabolic risk factors.

Combination therapy with an SGLT‐2 inhibitor and finerenone in DKD: Are we there yet?

“…2 For almost two decades, the only guidelinedirected pharmacological interventions to slow the progression of diabetic kidney disease (DKD) included the adequate glycemic and blood pressure control, as well as the inhibition of the renin-angiotensin system (RAS). 3 Despite optimal treatment, the residual cardiorenal risk of patients with CKD and T2D remained substantially elevated. A critical unmet need for the discovery and development of novel therapies to retard the progression of DKD and reduce the risk of cardiovascular morbidity and mortality persisted.…”

“…A critical unmet need for the discovery and development of novel therapies to retard the progression of DKD and reduce the risk of cardiovascular morbidity and mortality persisted. 3 Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors originally received regulatory approval for improving glycemic control in patients with T2D. 3 However, large outcome trials designed to test the cardiovascular safety of SGLT-2 inhibitors unexpectedly showed that cardiorenal protection is the most important effect of this novel antidiabetic drug class.…”

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Urine Albumin to Creatinine Ratio in Type 2 Diabetes Mellitus Patients and Medication Care

“…In the world, the number of DM patients had quadrupled in the past three decades, and meanwhile, DM was the ninth major cause of death, among which Asia had become the major area of the rapidly emerging T2DM global epidemic, and most T2DM patients always had at least one complication [ 23 ]. The complexity of T2DM treatment and care were very challenging because they involved the prevention of organ damage and complications [ 23 ], including chronic damage and dysfunction of various tissues, especially kidneys [ 4 ], blood vessels [ 5 ], nerves [ 6 ], and heart [ 7 ], among which kidney damage was one of the most common microvascular complications in DM patients, which brought great challenges to the treatment and nursing for DM patients.…”

“…In the world, the number of DM patients had quadrupled in the past three decades, and meanwhile, DM was the ninth major cause of death, among which Asia had become the major area of the rapidly emerging T2DM global epidemic, and most T2DM patients always had at least one complication [23]. The complexity of T2DM treatment and care were very challenging because they involved the prevention of organ damage and complications [23], including chronic damage and dysfunction of various tissues, especially kidneys [4], blood vessels [5], nerves [6], and heart [7], among SGLT-2 inhibitors were a group of antidiabetic drugs, which had the ability to reduce the blood sugar via inhibiting SGLT-2 [24]. Furthermore, except for lowering blood sugar [25][26][27][28][29][30], SGLT-2 inhibitors also had abilities to lose weight [24,31,32], reduce cardiovascular outcomes and mortality risk [33], and play renal protective effect [15].…”

“…What was more important was that DM could be complicated with multiple diseases significantly increasing the death risk of DM patient [ 1 ]. As everyone knows, long-term hyperglycemia would result in chronic damage and dysfunction of various tissues, especially kidneys [ 4 ], blood vessels [ 5 ], nerves [ 6 ], and heart [ 7 ], among which kidney damage was one of the most common microvascular complications in DM patients, which brought great challenges to the treatment and nursing for DM patients.…”