From the Guidelines
SGLT2 inhibitors should not be discontinued in patients with a GFR less than 20 mL/min/1.73m², but rather, their use should be individualized, considering the potential benefits of reducing CKD progression and cardiovascular events, as well as the risk of adverse effects, as recommended by the most recent guidelines 1. This includes medications such as empagliflozin (Jardiance), dapagliflozin (Farxiga), canagliflozin (Invokana), and ertugliflozin (Steglatro). The glucose-lowering effect of SGLT2 inhibitors is indeed blunted with reduced kidney function, but their use has been shown to have beneficial effects on CKD progression and cardiovascular outcomes, even in patients with eGFR <20 mL/min/1.73m², as noted in the guidelines 1. However, it is essential to carefully weigh the potential benefits against the risks of adverse effects, such as volume depletion, acute kidney injury, and electrolyte imbalances, and to regularly monitor kidney function in these patients. Some studies suggest that SGLT2 inhibitors may be more useful for patients at high risk of CKD progression, such as those with albuminuria or a history of documented eGFR loss 1. In patients with a GFR less than 20 mL/min/1.73m², alternative diabetes medications, such as insulin, certain GLP-1 receptor agonists, or dipeptidyl peptidase-4 inhibitors, may be considered, but the decision to use SGLT2 inhibitors should be made on a case-by-case basis, taking into account the individual patient's characteristics and medical history. Regular monitoring of kidney function is essential for all patients on SGLT2 inhibitors, with GFR checks recommended at least annually or more frequently in those with declining kidney function. Key considerations for the use of SGLT2 inhibitors in patients with CKD include:
- The potential benefits of reducing CKD progression and cardiovascular events
- The risk of adverse effects, such as volume depletion, acute kidney injury, and electrolyte imbalances
- The need for regular monitoring of kidney function
- The importance of individualizing treatment decisions based on the patient's medical history and characteristics. The most recent guidelines recommend the use of SGLT2 inhibitors in adults with type 2 diabetes who have CKD, with confirmed eGFR of 20–60 mL/min per 1.73 m² and/or albuminuria, for minimizing progression of CKD, reduction in cardiovascular events, and reduction in hospitalizations for HF 1.
From the Research
Effects of SGLT2 Inhibitors on Patients with Low GFR
- The use of SGLT2 inhibitors in patients with a very low Glomerular Filtration Rate (GFR) is not encouraged due to an initial dip in GFR 2.
- However, SGLT2 inhibitors have been shown to exert nephroprotective effects in people with type 2 diabetes, slowing the decline in GFR and reducing the onset of microalbuminuria and proteinuria 2.
- A study found that 6-week treatment with the SGLT2 inhibitor dapagliflozin did not affect proteinuria in patients with chronic kidney disease without diabetes, but did induce an acute and reversible decline in measured GFR (mGFR) 3.
Considerations for Patients with Low GFR
- SGLT2 inhibitors can be used in patients with an estimated GFR as low as 30 mL/min/1.73 m2, but caution is advised when initiating therapy in patients with a very low GFR 4.
- The benefits of SGLT2 inhibitors in reducing the risk of kidney outcomes have been observed in patients with a wide range of eGFR categories, including eGFR <45 mL/min/1.73 m2 5.
- However, introduction of an SGLT2 inhibitor in patients with a very low GFR is not encouraged due to an initial dip in GFR, and it is prudent to discontinue therapy if there is an acute renal event, hypovolaemia, or hypotension 2.
Key Findings
- SGLT2 inhibitors have been shown to reduce the risk of adverse kidney outcomes, including eGFR decline >50%, end-stage kidney disease, and all-cause mortality, compared to other glucose-lowering therapies 5.
- The nephroprotective effects of SGLT2 inhibitors are thought to be mediated by a range of mechanisms, including tubuloglomerular feedback, improved tubular oxygenation and metabolism, and reduced renal inflammation and fibrosis 2.