From the Guidelines
Steglatro (ertugliflozin) is not currently FDA-approved for chronic kidney disease (CKD), but Farxiga (dapagliflozin), Invokana (canagliflozin), and Jardiance (empagliflozin) are approved for CKD treatment. Among SGLT2 inhibitors, these three medications have received FDA approval for CKD. Farxiga is approved to reduce the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with CKD 1. Invokana is approved to reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in patients with type 2 diabetes and diabetic nephropathy with albuminuria. Jardiance received approval for CKD in 2023 to reduce the risk of sustained eGFR decline and end-stage kidney disease in adults with CKD at risk of progression 1.
The selection of specific SGLT2 inhibitors may depend on comorbidity and CKD stage, with SGLT2 inhibitors being more useful for individuals at high risk of CKD progression, such as those with albuminuria or a history of documented eGFR loss 1. The recommended eGFR level for SGLT2 inhibitor use has been lowered to >20 mL/min/1.73 m², based on subgroup analyses from the DAPA-CKD and EMPEROR heart failure trials, which suggest that SGLT2 inhibitors are safe and effective at eGFR levels >20 mL/min/1.73 m² 1.
Key points to consider when using SGLT2 inhibitors for CKD treatment include:
- Typical doses for CKD are dapagliflozin 10mg daily, canagliflozin 100mg daily, and empagliflozin 10mg daily
- SGLT2 inhibitors work by inhibiting sodium-glucose cotransporter-2 in the kidneys, providing renal protection through multiple mechanisms including reduced hyperfiltration, decreased albuminuria, and anti-inflammatory effects
- It is reasonable to continue SGLT2 inhibitor treatment even if the eGFR falls below 20 mL/min/1.73 m², unless it is not tolerated or kidney replacement therapy is initiated 1
From the FDA Drug Label
A 26-week placebo-controlled study of 313 patients with Stage 3 Chronic Kidney Disease (eGFR ≥30 to less than 60 mL/min/1.73 m2) treated with STEGLATRO did not demonstrate improvement in glycemic control. No dosage adjustment is needed in patients with eGFR ≥45 mL/min/1.73 m2.
Steglatro (ertugliflozin) is not specifically approved for Chronic Kidney Disease (CKD). However, it can be used in patients with eGFR ≥45 mL/min/1.73 m2 without dosage adjustment.
- Other SGLT2 inhibitors that may be used in patients with CKD include:
- Canagliflozin: approved for use in patients with eGFR ≥45 mL/min/1.73 m2
- Dapagliflozin: approved for use in patients with eGFR ≥45 mL/min/1.73 m2
- Empagliflozin: approved for use in patients with eGFR ≥45 mL/min/1.73 m2 2
From the Research
SGLT2 Inhibitors and CKD
- SGLT2 inhibitors, including ertugliflozin, have been shown to have renoprotective effects 3, 4, 5
- Ertugliflozin, also known as Steglatro, has been evaluated in patients with stage 3 chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) 4
- The VERTIS RENAL randomized study found that ertugliflozin had an acceptable safety profile and reduced blood glucose and body weight in patients with T2DM and stage 3 CKD 4
Ertugliflozin and Kidney Outcomes
- The VERTIS CV trial found that ertugliflozin reduced the risk of kidney composite outcomes, including doubling of serum creatinine, renal dialysis/transplant, or renal death 5
- Ertugliflozin was also associated with preservation of estimated glomerular filtration rate (eGFR) and reduced urinary albumin/creatinine ratio (UACR) 5
- The effects of ertugliflozin on kidney outcomes were consistent across subgroups, with a suggested larger effect observed in patients with macroalbuminuria and high/very high-risk CKD 5
Available SGLT2 Inhibitors
- Four SGLT2 inhibitors are currently commercially available: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin 3, 6
- These inhibitors have been shown to have favorable effects on glycated hemoglobin, body weight, blood pressure, and lipid profile, as well as cardioprotective and renoprotective effects 3, 6