From the Guidelines
SGLT2 inhibitors are recommended for individuals with CKD, particularly those with type 2 diabetes, to reduce CKD progression and cardiovascular events, and can be used in patients with an eGFR as low as 20 mL/min/1.73 m2. The use of SGLT2 inhibitors in CKD management has been supported by recent studies, including the EMPA-KIDNEY trial, which showed efficacy in participants with eGFR as low as 20 mL/min/1.73 m2 1. The typical dosing for SGLT2 inhibitors includes empagliflozin 10-25mg daily, dapagliflozin 10mg daily, or canagliflozin 100-300mg daily.
Key benefits of SGLT2 inhibitors in CKD management include:
- Slowing CKD progression
- Reducing the risk of kidney failure
- Providing cardiovascular protection by reducing heart failure hospitalizations and cardiovascular death
- Reducing intraglomerular pressure, improving tubuloglomerular feedback, decreasing inflammation, and enhancing energy efficiency in kidney cells
When initiating SGLT2 inhibitors, patients should be monitored for potential side effects, including:
- Genital mycotic infections
- Urinary tract infections
- Volume depletion
The most recent guidelines recommend the use of SGLT2 inhibitors in individuals with CKD, particularly those with type 2 diabetes, to reduce CKD progression and cardiovascular events, with an eGFR ≥20 mL/min/1.73 m2 1. This recommendation is based on the latest evidence from studies such as the EMPA-KIDNEY trial and the DECLARE-TIMI 58 trial, which demonstrated the effectiveness of SGLT2 inhibitors in reducing CKD progression and cardiovascular events in patients with CKD 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) • To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. (1) • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors (1) • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. (1)
The role of SGLT2 inhibitors in managing Chronic Kidney Disease (CKD) is to:
- Reduce the risk of sustained eGFR decline and end-stage kidney disease
- Reduce the risk of cardiovascular death and hospitalization for heart failure in adults with CKD at risk of progression 2 Key points to consider:
- Dapagliflozin is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2 2
- Dapagliflozin is not expected to be effective in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for the treatment of kidney disease 2
From the Research
Role of SGLT2 Inhibitors in CKD Management
- SGLT2 inhibitors have emerged as a promising therapeutic option for managing Chronic Kidney Disease (CKD) in patients with and without type 2 diabetes (T2D) 3, 4, 5.
- These inhibitors have been shown to slow disease progression, reduce the risk of end-stage kidney disease, and lower the risk of cardiovascular disease and all-cause mortality in patients with CKD 3, 6, 7.
Mechanisms and Benefits
- SGLT2 inhibitors work by inhibiting sodium and glucose reabsorption in the early proximal tubule of the renal nephron, which helps to reduce intraglomerular pressure and hyperfiltration 6, 7.
- The use of SGLT2 inhibitors has been associated with a reduced risk of CKD progression, as well as a lower risk of serious falls in kidney function and cardiovascular events 3, 4, 5, 7.
Clinical Evidence and Guidelines
- Several randomized controlled trials, including CREDENCE, DAPA-CKD, and EMPA-KIDNEY, have demonstrated the efficacy of SGLT2 inhibitors in slowing CKD progression and reducing the risk of adverse outcomes 3, 4, 5, 7.
- Recent guidelines, such as the KDIGO Guidelines, recommend the use of SGLT2 inhibitors as first-line therapy in patients with CKD, alongside other evidence-based treatments 7.
Prescribing Considerations
- SGLT2 inhibitors can be used in patients with CKD, regardless of diabetes status, and should be considered as an additional treatment option for CKD management in primary care 5.
- Concerns regarding safety appear unfounded, as the risk of acute kidney injury, hyperkalaemia, and major acute cardiovascular events is lower following SGLT2 inhibition 7.