Can a 90-year-old woman with Impaired renal function (GFR 15), Diabetes Mellitus (DM), Hypertension (HTN), and proteinuria (0.25g/24 hours) be treated with Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors?

From the Guidelines

SGLT2 inhibitors are not recommended for a 90-year-old woman with a GFR of 15 and diabetes, hypertension, and proteinuria. According to the most recent and highest quality study 1, SGLT2 inhibitors are recommended for patients with type 2 diabetes, chronic kidney disease, and an eGFR ≥20 ml/min per 1.73 m². However, this patient's GFR of 15 indicates severe kidney impairment, which is below the recommended threshold.

Key Considerations

• Most SGLT2 inhibitors (including empagliflozin, canagliflozin, and dapagliflozin) are contraindicated when GFR falls below 30 ml/min, as stated in the 2020 expert consensus decision pathway 1.
• At this level of kidney function, these medications lose their glucose-lowering efficacy and carry increased risks of adverse effects such as volume depletion, hypotension, and acute kidney injury, which would be particularly concerning in an elderly patient.
• The KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease recommends continuing SGLT2i even if the eGFR falls below 20 ml/min per 1.73 m², unless it is not tolerated or kidney replacement therapy is initiated 1. However, this patient's GFR is significantly lower, and the risks associated with SGLT2 inhibitors outweigh the potential benefits.

Alternative Treatment Options

• Alternative diabetes medications with better safety profiles in severe kidney disease would be more appropriate, such as:
  • Certain DPP-4 inhibitors (linagliptin requires no dose adjustment in kidney disease)
  • Certain GLP-1 receptor agonists
  • Carefully dosed insulin
• A nephrology consultation would be advisable to help manage both her diabetes and kidney disease, considering her advanced age and the need for careful consideration of hypoglycemia risk and less stringent glycemic targets.

From the FDA Drug Label

To reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria ( 1). 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( 1).

The patient has an eGFR of 15, which is less than 30 mL/min/1.73 m^2. SGLT2 inhibitors, such as canagliflozin, are not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus and an eGFR less than 30 mL/min/1.73 m^2 2.

• The patient's impaired renal function (GFR 15) is a contraindication for the use of SGLT2 inhibitors to improve glycemic control.
• The patient's diabetes mellitus, hypertension, and proteinuria are relevant conditions, but the primary concern is the patient's impaired renal function.

From the Research

Patient Characteristics

• The patient is a 90-year-old woman with impaired renal function (GFR 15)
• She has Diabetes Mellitus (DM), Hypertension (HTN), and proteinuria (0.25g/24 hours)

SGLT2 Inhibitors and Renal Function

• The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, requiring dosage adjustments or restrictions with moderate-to-severe renal dysfunction 3
• Dapagliflozin and canagliflozin are not recommended for use in patients with eGFR<60 and <45mL/min/1.73m(2), respectively 4
• The efficacy of SGLT2 inhibitors is affected by renal function, but some SGLT2 inhibitors can still induce significant HbA1c reduction even in mild and moderate renal impairment 5

Safety Concerns

• SGLT2 inhibitors are associated with an increased risk of genitourinary infections, volume depletion, and euglycemic ketoacidosis 6, 7
• Hospitalized patients treated with SGLT2 inhibitors are at increased risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections 7

Treatment Considerations

• SGLT2 inhibitors should be avoided for the inpatient management of hyperglycemia due to significant safety concerns 7
• They can be considered for the treatment of congestive heart failure, but should be started close to or at the time of discharge 7
• The use of SGLT2 inhibitors in patients with severe renal impairment (GFR 15) is not recommended due to the increased risk of adverse events and the decreased efficacy of the medication 3, 4