What is Empagliflozin (SGLT2 inhibitor)?

Empagliflozin: A Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor

Empagliflozin is a highly selective SGLT2 inhibitor that reduces glucose reabsorption in the kidneys, increases urinary glucose excretion, and provides significant cardiovascular and renal benefits beyond glycemic control in patients with type 2 diabetes. 1

Mechanism of Action

Empagliflozin works through a unique insulin-independent mechanism:

• Selectively inhibits SGLT2, the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into circulation 1
• Reduces renal glucose reabsorption and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion 1
• Produces approximately 64-78 grams of urinary glucose excretion per day at therapeutic doses 1
• Acts independently of β-cell function and insulin secretion, making it effective regardless of diabetes duration 2

Clinical Benefits

Empagliflozin offers multiple benefits beyond glycemic control:

Cardiovascular Benefits

• Reduces major adverse cardiovascular events (MACE) by 14% in patients with established cardiovascular disease 2
• Decreases cardiovascular death by 38% in high-risk patients 2
• Reduces hospitalization for heart failure by 35% 2
• Was the first SGLT2 inhibitor specifically approved by the FDA to reduce cardiovascular death risk in adults with type 2 diabetes and established cardiovascular disease 2, 3

Renal Benefits

• Improves kidney structure and function by reducing renal cortical hypoxia 2
• Decreases the burden on proximal tubular epithelial cells from reabsorbing large amounts of glucose 2
• Can be used in patients with eGFR ≥30 mL/min/1.73 m² for cardiovascular benefits 3

Metabolic Benefits

• Reduces HbA1c by approximately 0.5-1.0% 3
• Promotes weight reduction of 1.5-3.5 kg 3
• Lowers systolic blood pressure by 3-5 mmHg 3
• Improves insulin sensitivity and β-cell function by reducing glucotoxicity 4

Pharmacokinetic Properties

• Rapidly absorbed after oral administration with peak plasma concentrations at approximately 1.5 hours 1
• Exhibits biphasic elimination with a terminal half-life of 10.3-18.8 hours with multiple dosing 5
• Shows linear pharmacokinetics with respect to time 1
• Can be administered with or without food 1
• Highly protein-bound (86.2%) 1
• No major metabolites detected in human plasma; primarily eliminated as glucuronide conjugates 1

Dosage and Administration

• Available as 10 mg and 25 mg oral tablets 1
• Standard dosing for patients with eGFR ≥60 mL/min/1.73 m² 3
• Should be used with caution in patients with renal insufficiency (GFR <45 mL/min/1.73 m²) 2
• Not recommended for glycemic control in patients with eGFR <45 mL/min/1.73 m², though cardiovascular benefits may persist down to eGFR of 30 mL/min/1.73 m² 3

Safety Profile and Adverse Effects

• Low risk of hypoglycemia when used alone (not with insulin or insulin secretagogues) 3
• Common adverse effects include:
  • Genitourinary tract infections 3
  • Volume depletion 3
• Rare but serious adverse effects:
  • Euglycemic diabetic ketoacidosis 3
  • Acute kidney injury 3

Clinical Considerations

• Empagliflozin has the highest SGLT2 specificity among clinically used SGLT2 inhibitors 6
• Can be used without regard to diabetes duration, provided renal function is acceptable 2
• May improve cardiac energy status via enhanced mitochondrial ATP production 7
• Provides benefits in non-diabetic, obese, and hypertensive patients with high-risk factor profiles 2

Contraindications

• History of serious hypersensitivity reaction to the drug 2
• Severe renal impairment, end-stage renal disease, or dialysis 2

Empagliflozin represents a significant advancement in type 2 diabetes management with its unique mechanism of action and proven benefits for reducing cardiovascular mortality and morbidity beyond glycemic control.