What are the recommendations for initiating Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors in patients with Impaired renal function, specifically those with a Glomerular Filtration Rate (GFR) less than 30?

From the Guidelines

SGLT2 inhibitors are not recommended for initiation in patients with an eGFR less than 30 ml/min/1.73m², but can be considered for patients with diabetic kidney disease and an eGFR of at least 20 ml/min/1.73m², as they have been shown to reduce CKD progression and cardiovascular events 1. When considering the use of SGLT2 inhibitors in patients with chronic kidney disease (CKD), it is essential to weigh the potential benefits against the risks. The evidence suggests that SGLT2 inhibitors can provide cardiovascular and kidney-protective effects, even at lower eGFR levels, through mechanisms independent of glycemic control 1. Some key points to consider when initiating SGLT2 inhibitors in patients with CKD include:

• Eligible patients should have an eGFR ≥20 ml/min/1.73m² and high priority features such as albuminuria or a history of documented eGFR loss 1
• The selection of specific agents may depend on comorbidity and CKD stage, with SGLT2 inhibitors being more useful for patients at high risk of CKD progression 1
• Common SGLT2 inhibitors include empagliflozin (10-25mg daily), dapagliflozin (5-10mg daily), canagliflozin (100-300mg daily), and ertugliflozin (5-15mg daily) 1
• When initiating these medications, monitor for genital mycotic infections, urinary tract infections, volume depletion, and diabetic ketoacidosis, especially in vulnerable patients 1 It is crucial to note that the glucose-lowering efficacy of SGLT2 inhibitors is reduced as eGFR declines, but kidney and cardiovascular benefits are preserved 1. Therefore, the use of SGLT2 inhibitors in patients with CKD should be individualized, taking into account the patient's specific clinical characteristics and the potential benefits and risks of treatment 1.

From the FDA Drug Label

INVOKANA is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m^2. In patients with eGFR less than 30 Initiation is not recommended Use of DAPAGLIFLOZIN TABLETS for glycemic control in patients without established CV disease or CV risk factors is not recommended when eGFR is less than 45 mL/min/1.73 m^2

Recommendation:

• Do not initiate SGLT2 inhibitors, such as canagliflozin or dapagliflozin, in patients with a GFR less than 30 mL/min/1.73 m^2 for glycemic control.
• For patients with established CV disease or CV risk factors, the decision to initiate SGLT2 inhibitors should be made on a case-by-case basis, considering the potential benefits and risks.
• The FDA drug label for canagliflozin 2 and dapagliflozin 3 provides guidance on dosage adjustments and contraindications for patients with renal impairment.

From the Research

SGLT2 Inhibitors and Renal Function

• The use of SGLT2 inhibitors in patients with type 2 diabetes and renal disease has been studied extensively 4, 5, 6, 7, 8.
• These inhibitors have been shown to have renoprotective effects, including reducing the risk of development or worsening of albuminuria, a marker of renal damage 8.
• The glucose-lowering efficacy of SGLT2 inhibitors is dependent on renal function, but the cardiovascular and renal benefits appear to be maintained to estimated glomerular filtration levels as low as 30 mL/min/1.73 m2 8.

Starting SGLT2 Inhibitors with GFR Less Than 30

• There is evidence to suggest that SGLT2 inhibitors can be beneficial for patients with compromised renal function, including those with a GFR less than 30 4, 5, 7.
• A meta-analysis showed that SGLT2 inhibitors enhanced kidney function more than controls, and had the potential to prevent eGFR reduction and improve renal function in patients with compromised renal function 4.
• However, the decision to start SGLT2 inhibitors in patients with a GFR less than 30 should be made on a case-by-case basis, taking into account the individual patient's clinical characteristics and medical history 8.

Mechanisms of SGLT2 Inhibitors

• SGLT2 inhibitors work by inhibiting the coupled reabsorption of sodium and glucose from the proximal tubules, increasing renal glucose and sodium excretion 6.
• They also have widespread renal effects, including inhibition of the sodium:proton exchanger, and can activate the tubuloglomerular feedback response to correct glomerular hyperfiltration 6.
• The renoprotective effects of SGLT2 inhibitors involve blood glucose-dependent and independent effects, and extend to patients with chronic kidney disease (CKD) 7.