Should an SGLT2 inhibitor be added to the treatment regimen of a patient with impaired renal function, on metformin, with a history of hyperglycemia, HFpEF, and AF?

From the Guidelines

Yes, an SGLT2 inhibitor should be added to the treatment regimen of a patient with impaired renal function, on metformin, with a history of hyperglycemia, HFpEF, and AF.

Key Considerations

• The patient has a history of HFpEF, and SGLT2 inhibitors have been shown to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes and established cardiovascular disease or increased cardiovascular risk 1.
• The patient is already on metformin, which is a reasonable first-line therapy for patients with HF and CKD, as long as eGFR exceeds 30 mL·min −1·1.73 m² 1.
• The use of SGLT2 inhibitors in patients with CKD seems promising given their HF benefit and potential for renal protection, although results of ongoing RCTs are needed to ensure they are safe to use at lower eGFR levels 1.

Important Details

• The EMPA-REG OUTCOME trial, CANVAS Program, and DAPA-HF study have demonstrated the effectiveness of SGLT2 inhibitors in reducing the risk of hospitalization for heart failure in patients with type 2 diabetes and established cardiovascular disease or increased cardiovascular risk 1.
• The SCORED trial has also shown that the SGLT1/2 inhibitor sotagliflozin reduces the primary outcome of death from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure in people with type 2 diabetes, CKD, and risk for cardiovascular disease 1.
• The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommend the use of SGLT2 inhibitors in people with established CVD, CKD, and HF to reduce MACE, HF, and improve kidney outcomes 1.

Renal Function Considerations

• The patient's impaired renal function should be taken into account when selecting an SGLT2 inhibitor, as some studies have shown that these agents can be used safely in patients with eGFR as low as 20 mL·min−1·1.73 m−2 1.
• However, the patient's eGFR should be closely monitored, and the dose of the SGLT2 inhibitor may need to be adjusted based on renal function 1.

Medication Selection

• The choice of SGLT2 inhibitor should be based on the patient's individual characteristics, such as renal function, cardiovascular risk factors, and concomitant medications 1.
• Empagliflozin, canagliflozin, and dapagliflozin are all effective SGLT2 inhibitors that have been shown to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes and established cardiovascular disease or increased cardiovascular risk 1.

From the Research

Patient Profile

• The patient has impaired renal function
• The patient is currently on metformin
• The patient has a history of hyperglycemia, HFpEF, and AF

SGLT2 Inhibitors and Renal Function

• SGLT2 inhibitors may have renal protective effects in people with impaired kidney function 2
• In populations with renal impairment, SGLT2 inhibition compared with placebo was consistently associated with an initial decrease in eGFR followed by an increase and return to baseline levels 2
• SGLT2 inhibitors are associated with decreased urine albumin, improved albuminuria, slowed progression to macroalbuminuria, and reduced the risk of worsening renal impairment, the initiation of kidney transplant, and death from renal disease 2

SGLT2 Inhibitors and Cardiovascular Outcomes

• SGLT2 inhibitors demonstrate cardiovascular and renal benefits in patients with heart failure (HF) 3
• SGLT2i treatment was associated with lower incidences of the composite outcomes of cardiovascular death or hospitalization for HF, cardiovascular death, and serious decrease in renal function 3
• SGLT2i treatment contributed to better cardiovascular and renal outcomes in patients with HF, regardless of the presence or absence of DM 3

Safety Considerations

• SGLT2 inhibitors are associated with a higher incidence of volume depletion 3
• SGLT2 inhibitors may increase the risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections, particularly in the inpatient setting 4
• The use of SGLT2 inhibitors in the inpatient management of hyperglycemia is not recommended due to safety concerns 4

Treatment Considerations

• SGLT2 inhibitors can be used in combination with metformin for the treatment of hyperglycemia in type 2 diabetes 5, 6
• SGLT2 inhibitors may be considered for the treatment of congestive heart failure, but should be started close to or at the time of discharge 4