What is the creatinine cut-off for initiating Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes?

From the Guidelines

The general creatinine cut-off for initiating SGLT2 inhibitors in patients with type 2 diabetes is an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73m², as recommended by the KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease 1.

Key Considerations for SGLT2 Inhibitor Initiation

• The choice of an SGLT2 inhibitor should prioritize agents with documented kidney or cardiovascular benefits and take eGFR into account 1.
• It is reasonable to withhold SGLT2 inhibitors during times of prolonged fasting, surgery, or critical medical illness, as patients may be at greater risk for ketosis 1.
• For patients at risk of hypovolemia, consider decreasing thiazide or loop diuretic dosages before commencement of SGLT2 inhibitor treatment, advise patients about symptoms of volume depletion and low blood pressure, and follow up on volume status after drug initiation 1.
• A reversible decrease in the eGFR with commencement of SGLT2 inhibitor treatment may occur and is generally not an indication to discontinue therapy 1.
• Once an SGLT2 inhibitor is initiated, it is reasonable to continue the medication even if the eGFR falls below 20 mL/min/1.73m², unless it is not tolerated or kidney replacement therapy is initiated 1.

Additional Guidance from Recent Studies

• The 2022 guideline recommended use of SGLT2 inhibitors, such as empagliflozin and dapagliflozin, with eGFR 25–45 mL/min/1.73m² for kidney/heart failure outcomes 1.
• Empagliflozin can be started with eGFR >30 mL/min/1.73m², though pivotal trials for each included participants with eGFR <30 mL/min/1.73m² and demonstrated benefit in subgroups with low eGFR 1.
• SGLT2 inhibitors have been observed to have consistent efficacy and safety across studied ranges of eGFR, and can be initiated for most patients with type 2 diabetes, chronic kidney disease, and eGFR ≥20 mL/min/1.73m² 1.
• SGLT2 inhibitor initiation is associated with a reversible decline in eGFR, but this generally does not require drug discontinuation, and SGLT2 inhibitor use appears to protect patients from acute kidney injury (AKI) 1.

Practical Approach to Initiating SGLT2 Inhibitors

• Eligible patients include those with eGFR ≥20 mL/min/1.73m² and high priority features such as albumin-creatinine ratio (ACR) ≥200 mg/g 1.
• Potential contraindications include genital infection risk, diabetic ketoacidosis, foot ulcers, and immunosuppression 1.
• Education on hypoglycemia, volume depletion, and sick day protocol is essential for patients initiating SGLT2 inhibitors 1.

From the Research

Creatinine Cut-Off for SGLT2-Inhibitors

• The creatinine cut-off for initiating Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes is not explicitly stated as a creatinine value, but rather as an estimated glomerular filtration rate (eGFR) in the provided studies.
• According to 2, SGLT2 inhibitors should be considered for patients with type 2 diabetes and chronic kidney disease having an eGFR ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g.
• 3 suggests that SGLT2 inhibitors are most effective if the eGFR is more than 60 ml per min per 1·73m2 at initiation.
• There is no direct mention of a creatinine cut-off value in the provided studies, but rather an emphasis on eGFR and UACR as criteria for initiating SGLT2 inhibitors.
• The studies focus on the benefits of SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease, including reduced cardiovascular risk and slowed progression of kidney disease, as discussed in 4, 5, and 6.