From the Guidelines
SGLT2 inhibitors are recommended for patients with chronic kidney disease (CKD) to reduce CKD progression and cardiovascular events, and should be used in patients with an eGFR ≥20 mL/min/1.73 m² and urine albumin ranging from normal to 200 mg/g creatinine, as supported by the most recent evidence from 1.
Key Points
- SGLT2 inhibitors have been shown to provide renoprotection through multiple mechanisms, including reduced hyperfiltration, decreased tubular workload, improved tubuloglomerular feedback, and anti-inflammatory effects 1.
- Medications like empagliflozin, dapagliflozin, and canagliflozin have demonstrated significant reductions in CKD progression, heart failure hospitalizations, and cardiovascular death 1.
- These medications are generally well-tolerated, but patients should be monitored for genital mycotic infections, urinary tract infections, and volume depletion, especially when starting therapy 1.
- SGLT2 inhibitors should be used cautiously in patients with eGFR below 30 ml/min/1.73m², and the decision to use them in patients with eGFR below 20 ml/min/1.73m² should be made on a case-by-case basis, considering the potential benefits and risks 1.
Benefits and Risks
- The benefits of SGLT2 inhibitors in patients with CKD include reduced CKD progression, cardiovascular events, and hospitalizations for heart failure 1.
- The risks associated with SGLT2 inhibitors include genital mycotic infections, urinary tract infections, and volume depletion, which can be mitigated with proper monitoring and patient education 1.
Clinical Considerations
- SGLT2 inhibitors should be considered part of standard care for most CKD patients, regardless of diabetes status, and should be used in conjunction with other kidney-protective therapies like ACE inhibitors or ARBs 1.
- The selection of specific SGLT2 inhibitors may depend on comorbidity and CKD stage, and patients with high risk of CKD progression may benefit from these medications the most 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 role of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, in Chronic Kidney Disease (CKD) is to:
- Reduce the risk of sustained eGFR decline
- Reduce the risk of end stage kidney disease
- Reduce the risk of cardiovascular death
- Reduce the risk of hospitalization for heart failure in adults with CKD at risk of progression 2 2.
From the Research
Role of SGLT2 Inhibitors in CKD
- SGLT2 inhibitors have emerged as a promising therapeutic option for patients with chronic kidney disease (CKD), including those with and without type 2 diabetes (T2D) 3, 4, 5.
- These inhibitors have been shown to slow disease progression, prevent the development of end-stage kidney disease, and reduce the risk of cardiovascular disease and all-cause mortality in patients with CKD 3, 6, 7.
Mechanism of Action
- SGLT2 inhibitors work by inhibiting sodium and glucose reabsorption in the early proximal tubule of the renal nephron, which helps to reduce kidney damage and slow disease progression 4, 6.
Clinical Trials and Outcomes
- Several clinical trials, including CREDENCE, DAPA-CKD, and EMPA-KIDNEY, have demonstrated the effectiveness of SGLT2 inhibitors in reducing the risk of kidney failure and cardiovascular events in patients with CKD 3, 4, 6, 7.
- These trials have shown that SGLT2 inhibitors can slow the decline in estimated glomerular filtration rate (eGFR) and reduce the incidence of serious kidney events, such as end-stage kidney disease and kidney failure 3, 6, 7.
Guideline Recommendations
- Recent guideline recommendations, including those from the Kidney Disease: Improving Global Outcomes (KDIGO) organization, suggest the use of SGLT2 inhibitors as first-line therapy in patients with CKD, alongside other treatments such as statins and renin-angiotensin-aldosterone system inhibitors 4, 5.
- However, despite these recommendations, SGLT2 inhibitors remain underutilized in the treatment of CKD, particularly in patients without T2D 4, 5.