What class of medication is Invokana (canagliflozin)?

Invokana (Canagliflozin) Medication Class

Invokana (canagliflozin) belongs to the sodium-glucose cotransporter-2 (SGLT2) inhibitor class of medications used for treating type 2 diabetes mellitus. 1

Mechanism of Action

• SGLT2 inhibitors work by inhibiting the sodium-glucose cotransporter-2 in the proximal tubule of the nephron, which is responsible for approximately 90% of urinary glucose reabsorption 2
• By inhibiting SGLT2, canagliflozin reduces renal glucose reabsorption, thereby increasing urinary glucose excretion and reducing blood glucose levels through an insulin-independent mechanism 1
• Canagliflozin also causes diuretic and natriuretic effects, weight loss, and lowering of systolic blood pressure beyond its glucose-lowering effects 2

Clinical Applications

• Indicated for improving glycemic control in adults with type 2 diabetes mellitus 1
• Has demonstrated cardiovascular benefits, including reduction in major adverse cardiovascular events (MACE) in patients with established atherosclerotic cardiovascular disease 2
• FDA-approved for reducing the risk of cardiovascular death in adults with type 2 diabetes and cardiovascular disease 2
• Provides renoprotective effects and is indicated to reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in patients with type 2 diabetes and diabetic nephropathy with albuminuria 1, 2

Pharmacological Characteristics

• Available in oral tablet formulations of 100 mg and 300 mg for once-daily administration 1
• Has a low risk of hypoglycemia when used as monotherapy due to its insulin-independent mechanism of action 2
• Efficacy is reduced in patients with renal impairment; not recommended for use when eGFR is below 30 mL/min/1.73 m² 1, 2
• Demonstrates intermediate to high glucose-lowering efficacy according to current diabetes treatment guidelines 2

Position in Diabetes Treatment Algorithm

• Often used as second-line therapy after metformin in patients with type 2 diabetes, particularly in those with established cardiovascular disease, heart failure, or chronic kidney disease 2
• Current guidelines recommend SGLT2 inhibitors like canagliflozin for patients with type 2 diabetes who have:
  • Established atherosclerotic cardiovascular disease 2
  • Heart failure, particularly with reduced ejection fraction 2
  • Chronic kidney disease with eGFR 30 to <90 mL/min/1.73 m² 2

Common Side Effects and Safety Considerations

• Most common adverse events include genital mycotic infections, urinary tract infections, and increased urination 1, 2
• Risk of diabetic ketoacidosis (DKA), including euglycemic DKA, though rare in type 2 diabetes 2
• Increased risk of volume depletion, particularly in elderly patients or those on diuretics 1
• Canagliflozin specifically has been associated with increased risk for lower limb amputations (FDA black box warning) 2
• Should be temporarily discontinued before scheduled surgery, during critical illness, or during prolonged fasting to reduce DKA risk 2

Distinguishing Features Within SGLT2 Inhibitor Class

• Canagliflozin was the first SGLT2 inhibitor approved in the United States 3
• Compared to other SGLT2 inhibitors, canagliflozin has greater potential for inhibiting SGLT1 receptors, which may contribute to some of its effects on intestinal glucose absorption 2
• The CREDENCE trial specifically demonstrated canagliflozin's benefits in patients with diabetic nephropathy, showing a 30% reduction in the composite renal outcome 2

Understanding the SGLT2 inhibitor class is essential for optimal management of type 2 diabetes, particularly given the significant cardiovascular and renal benefits these medications provide beyond glucose control.