What is the indication for Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors in Chronic Kidney Disease (CKD)?

From the Guidelines

SGLT2 inhibitors should be used in patients with chronic kidney disease (CKD) regardless of diabetes status, particularly those with an estimated glomerular filtration rate (eGFR) of 20-60 mL/min/1.73m² and albuminuria >200 mg/g, as they have been shown to slow CKD progression, reduce the risk of kidney failure, cardiovascular events, and hospitalization for heart failure 1.

Key Points

• The use of SGLT2 inhibitors in CKD is recommended for patients with an eGFR ≥20 ml/min per 1.73 m², with or without diabetes, as stated in the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease 1.
• Recommended medications include dapagliflozin 10 mg daily or empagliflozin 10 mg daily, which should be added to standard therapy including ACE inhibitors or ARBs.
• SGLT2 inhibitors work by reducing glomerular hyperfiltration, decreasing albuminuria, and providing cardiorenal protection through multiple mechanisms including reduced inflammation and oxidative stress.
• Common side effects include genital mycotic infections and volume depletion, and patients should be monitored for acute kidney injury, especially during illness that may cause dehydration.

Important Considerations

• SGLT2 inhibitors should not be initiated when eGFR is below 20 mL/min/1.73m², though they can be continued in patients already taking them if eGFR drops below this threshold, as stated in the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease 1.
• It is reasonable to withhold SGLT2i during times of prolonged fasting, surgery, or critical medical illness, and to consider decreasing thiazide or loop diuretic dosages before commencement of SGLT2i treatment to minimize the risk of volume depletion 1.
• The choice of an SGLT2i should prioritize agents with documented kidney or cardiovascular benefits, and take eGFR into account, as recommended in the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease 1.

From the FDA Drug Label

DAPAGLIFLOZIN TABLETS a sodium-glucose cotransporter 2 (SGLT2) inhibitor, are indicated: • To reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression (1)

The indication for Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, in Chronic Kidney Disease (CKD) is to reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with CKD at risk of progression 2. Key points:

• The drug is indicated for adults with CKD at risk of progression.
• The goal is to reduce the risk of CKD progression and related cardiovascular events.

From the Research

Indication for SGLT2 Inhibitors in CKD

The indication for Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors in Chronic Kidney Disease (CKD) is as follows:

• SGLT2 inhibitors are recommended as first-line therapy in patients with CKD, alongside statins, renin-angiotensin-aldosterone system inhibitors, and multifactorial risk factor management as indicated 3
• These inhibitors have been shown to slow the trajectory of kidney function decline and reduce the incidence of serious falls in kidney function in patients with CKD 3, 4, 5
• The use of SGLT2 inhibitors has been associated with a reduced risk of CKD progression, cardiovascular disease, and all-cause mortality in patients with CKD, with and without type 2 diabetes 6, 4, 5, 7

Patient Selection

The following patient populations may benefit from SGLT2 inhibitors:

• Patients with type 2 diabetes and CKD 3, 6, 4, 5, 7
• Patients with CKD without type 2 diabetes 4, 5
• Patients with heart failure and CKD, with or without type 2 diabetes 5, 7

Safety and Efficacy

The safety and efficacy of SGLT2 inhibitors in patients with CKD have been established in several studies:

• SGLT2 inhibitors have been shown to be effective in reducing hyperglycaemia, weight, and blood pressure in patients with CKD 6
• The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, but the glucose-lowering efficacy and safety are almost comparable in patients with mild CKD as in patients with normal kidney function 6
• Concerns regarding safety appear unfounded, as acute kidney injury, hyperkalaemia, major acute cardiovascular events, and cardiac death in patients with CKD appear to be lower following SGLT2 inhibition 3