Can SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors delay the progression of Chronic Kidney Disease (CKD)?

From the Guidelines

Yes, SGLT2 inhibitors can effectively delay the progression of Chronic Kidney Disease, as recommended for individuals with eGFR ≥20 mL/min/1.73 m², according to the most recent guidelines 1.

Key Points

• Medications in this class, including empagliflozin (Jardiance), canagliflozin (Invokana), dapagliflozin (Farxiga), and ertugliflozin (Steglatro), have demonstrated significant kidney-protective effects in clinical trials.
• The typical dosing is once daily (empagliflozin 10-25mg, canagliflozin 100-300mg, dapagliflozin 5-10mg, or ertugliflozin 5-15mg).
• These medications work by blocking glucose reabsorption in the proximal tubule of the kidney, which reduces glomerular hyperfiltration and decreases albuminuria.
• SGLT2 inhibitors also provide additional benefits including improved cardiovascular outcomes and reduced heart failure hospitalizations.
• Patients should be monitored for potential side effects including genital mycotic infections, urinary tract infections, and volume depletion.

Recommendations

• SGLT2 inhibitors are recommended for patients with CKD who have an eGFR ≥20 mL/min/1.73 m², as stated in the latest guidelines 1.
• They can be used in patients with or without diabetes, as their kidney-protective effects appear to be independent of their glucose-lowering properties.
• The selection of specific agents may depend on comorbidity and CKD stage, with SGLT2 inhibitors being more useful for individuals at high risk of CKD progression (i.e., with albuminuria or a history of documented eGFR loss) 1.

From the FDA Drug Label

Canagliflozin increases the delivery of sodium to the distal tubule by blocking SGLT2-dependent glucose and sodium reabsorption. This is believed to increase tubuloglomerular feedback and reduce intraglomerular pressure.

The FDA drug label does not answer the question.

From the Research

SGLT2 Inhibitors and Chronic Kidney Disease

• SGLT2 inhibitors have been shown to delay the progression of Chronic Kidney Disease (CKD) in patients with and without type 2 diabetes mellitus 2, 3, 4, 5, 6.
• The mechanism of action of SGLT2 inhibitors involves blocking tubular SGLT2, which reduces glomerular pressure and filtration, and thereby reduces the physical stress on the filtration barrier 2.
• SGLT2 inhibitors also have anti-inflammatory, anti-fibrotic, and anti-senescence effects, which can help to preserve tubular function and glomerular filtration rate (GFR) in the long-term 2, 6.
• Clinical trials have demonstrated that SGLT2 inhibitors can reduce the risk of kidney disease progression, including a decrease in albuminuria and a slowing of the decline in estimated GFR 3, 4, 5.

Benefits of SGLT2 Inhibitors in CKD

• SGLT2 inhibitors have been shown to have a low risk of hypoglycemia and can provide additional benefits, including weight loss and improved blood pressure control 2, 3.
• The use of SGLT2 inhibitors in combination with other agents, such as glucagon-like peptide-1 receptor agonists (GLP-1-RAs) and novel mineralocorticoid receptor antagonists, may be considered to reduce residual albuminuria and cardiovascular risk 3.
• SGLT2 inhibitors have been recommended as first-line therapy in patients with CKD, alongside statins, renin-angiotensin-aldosterone system inhibitors, and multifactorial risk factor management as indicated 4.

Practical Considerations for Prescribing SGLT2 Inhibitors

• The anticipated acute decline in estimated GFR on initiation of SGLT2 inhibitors should be considered, and the lowest dosage used in clinical trials should be initiated 3.
• Volume status considerations and adverse event mitigation are also important when prescribing SGLT2 inhibitors 3.
• The potential benefits and harms of SGLT2 inhibitors should be carefully considered, and risk mitigation strategies should be implemented to minimize the risk of adverse events 5.