What is Bexagliflozin (Sodium-Glucose Cotransporter 2 inhibitor)?

Bexagliflozin: A Sodium-Glucose Cotransporter 2 Inhibitor

Bexagliflozin (BRENZAVVY™) is an FDA-approved SGLT2 inhibitor that works by inhibiting renal glucose reabsorption, increasing urinary glucose excretion, and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. 1, 2

Mechanism of Action

Bexagliflozin functions by:

• Inhibiting SGLT2, the renal transporter responsible for glucose reabsorption from glomerular filtrate
• Reducing renal threshold for glucose, thereby increasing urinary glucose excretion
• Working independently of β-cell function and insulin secretion, making it suitable for patients with type 2 diabetes regardless of disease duration 3, 1

Clinical Benefits

Bexagliflozin demonstrates several benefits:

• Reduces HbA1c by approximately 0.45% compared to placebo 4
• Promotes weight loss (average reduction of 1.77 kg) 4
• Lowers systolic blood pressure (average reduction of 4.11 mmHg) 4
• Reduces fasting plasma glucose 4

Like other SGLT2 inhibitors, bexagliflozin may provide cardiovascular and renal benefits, though specific outcome trials for bexagliflozin are still pending. Other SGLT2 inhibitors have demonstrated:

• Reduction in major adverse cardiovascular events 5
• Decreased hospitalization for heart failure 5
• Slowed progression of chronic kidney disease 3

Indications and Dosing

• FDA-approved in January 2023 for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes 2
• Standard oral dosing is 20 mg once daily 4
• Can be used in patients with eGFR ≥30 mL/min/1.73 m² 2

Contraindications and Precautions

Bexagliflozin is contraindicated in:

• Patients receiving dialysis 2
• Patients with type 1 diabetes 2
• Patients with eGFR <30 mL/min/1.73 m² 2

Common precautions associated with SGLT2 inhibitors include:

• Risk of intravascular volume contraction, particularly in patients with renal impairment, low systolic blood pressure, those on diuretics, or the elderly 5
• Increased risk of mycotic genital infections 5, 3
• Risk of euglycemic diabetic ketoacidosis, especially in vulnerable patients 5, 3
• Hypoglycemia risk when used with insulin or insulin secretagogues 5

Adverse Effects

The most common adverse effects include:

• Genitourinary tract infections, particularly mycotic infections 3
• Potential for volume depletion 5

Rare but serious adverse effects may include:

• Euglycemic ketoacidosis 5, 3
• Acute kidney injury 3

Clinical Context

Bexagliflozin is the fifth SGLT2 inhibitor approved by the FDA for type 2 diabetes management, following dapagliflozin, canagliflozin, empagliflozin, and ertugliflozin 6. While it shares the same mechanism of action as other SGLT2 inhibitors, long-term cardiovascular and renal outcome data specific to bexagliflozin are still being collected. Current evidence suggests its effects are consistent with other drugs in this class 7.

Practical Considerations

• SGLT2 inhibitors are generally not recommended for routine use in the hospital setting due to risk of euglycemic diabetic ketoacidosis and genitourinary infections 3
• Should be discontinued in patients at risk for lactic acidosis (acute kidney injury, hypoxia, shock) 3
• Bexagliflozin has been studied in patients with diabetes and CKD stage 3b and shown to be safe and effective in this population 7

Bexagliflozin represents an additional therapeutic option for managing patients with type 2 diabetes, with a mechanism of action and side effect profile consistent with other SGLT2 inhibitors.