Is it safe to use SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors in patients with preserved Ejection Fraction (EF) and moderate renal impairment?

From the Guidelines

SGLT2 inhibitors can be safely used in patients with preserved ejection fraction and moderate renal impairment, as they provide cardiovascular and renal protection benefits independent of their glucose-lowering effects, as demonstrated in the most recent study 1. The use of SGLT2 inhibitors in patients with moderate renal impairment (eGFR 30-60 ml/min/1.73m²) is supported by recent guidelines, which suggest that these medications can be used with caution in this population, with no dose adjustment typically needed, though efficacy for glycemic control may be reduced 1. Some key considerations when using SGLT2 inhibitors in patients with preserved ejection fraction and moderate renal impairment include:

• Monitoring renal function and maintaining adequate hydration to minimize the risk of adverse effects such as volume depletion and acute kidney injury 1
• Being vigilant for potential side effects, including genital mycotic infections, urinary tract infections, and hypoglycemia 1
• Considering the potential benefits of SGLT2 inhibitors in reducing the risk of major cardiovascular adverse events, renal events, and hospitalization rates for heart failure, as demonstrated in recent studies 1 The cardioprotective effects of SGLT2 inhibitors likely stem from multiple mechanisms, including improved cardiac energetics, reduced inflammation, and decreased cardiac preload and afterload, while the renal protective effects appear to involve reduced intraglomerular pressure and other mechanisms that slow progression of kidney disease 1. Overall, the use of SGLT2 inhibitors in patients with preserved ejection fraction and moderate renal impairment is supported by recent evidence and guidelines, and these medications can be a valuable addition to the treatment regimen for these patients, as long as they are used with caution and careful monitoring 1.

From the FDA Drug Label

The efficacy and safety of INVOKANA for glycemic control were evaluated in a trial that included adult patients with moderate renal impairment (eGFR 30 to less than 50 mL/min/1.73 m 2) [see Clinical Studies (14. 1)] . Patients with renal impairment using INVOKANA for glycemic control may also be more likely to experience hypotension and may be at higher risk for acute kidney injury [see Warnings and Precautions (5. 3)] .

The use of SGLT2 inhibitors, such as canagliflozin, may be considered in patients with preserved Ejection Fraction (EF) and moderate renal impairment. However, caution is advised due to the potential increased risk of hypotension and acute kidney injury in patients with renal impairment.

• Patients with moderate renal impairment may experience less overall glycemic efficacy.
• Monitoring for signs and symptoms of volume depletion, hypotension, and acute kidney injury is recommended.
• The safety and efficacy of SGLT2 inhibitors in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m 2) have not been established 2.

From the Research

Safety of SGLT2 Inhibitors in Patients with Preserved EF and Moderate Renal Impairment

• The use of SGLT2 inhibitors in patients with type 2 diabetes and moderate renal impairment has been associated with renal protective effects 3.
• Studies have shown that SGLT2 inhibitors can prevent further renal function deterioration and death from kidney disease in patients with diabetes and renal impairment 3, 4.
• In patients with preserved ejection fraction (EF) and moderate renal impairment, SGLT2 inhibitors may be beneficial in reducing the risk of worsening renal impairment and cardiovascular events 3, 5.
• However, it is essential to carefully evaluate the patient's renal function and adjust the dose of the SGLT2 inhibitor accordingly, as renal impairment can affect the drug's efficacy and safety 3, 6.

Renal Impairment and SGLT2 Inhibitors

• Moderate renal impairment is defined as an estimated glomerular filtration rate (eGFR) of ≥30 and <60ml/min/1.73m2 and/or UACR>300 and ≤5000mg/g 3.
• SGLT2 inhibitors have been shown to be effective in patients with moderate renal impairment, but their use in patients with severe renal impairment requires caution and careful dose adjustment 3, 6.
• The renal protective effects of SGLT2 inhibitors are thought to be due to their ability to reduce glucose reabsorption in the proximal renal tubules, which can help to slow the progression of renal disease 3, 4.

Clinical Trials and Evidence

• Several clinical trials, including the EMPA-REG OUTCOME TRIAL, DECLARE-TIMI 58, CANVAS, and VERTIS-CV studies, have demonstrated the cardiovascular and renal benefits of SGLT2 inhibitors in patients with diabetes and cardiovascular disease 4, 5.
• The DAPA-HF study and the EMPEROR-REDUCED TRIAL have shown that SGLT2 inhibitors can be used to treat patients with heart failure, with or without diabetes 4, 5.
• The use of SGLT2 inhibitors in patients with preserved EF and moderate renal impairment is supported by the available evidence, but further studies are needed to fully understand their effects in this population 3, 5.