What are examples of Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors?

Examples of SGLT2 Inhibitors

The commercially available SGLT2 inhibitors include dapagliflozin, empagliflozin, canagliflozin, ertugliflozin, and sotagliflozin. 1

Available SGLT2 Inhibitors and Their Characteristics

SGLT2 inhibitors work by inhibiting renal tubular SGLT2, which is responsible for glucose reabsorption from urine. This mechanism:

• Reduces the renal glucose threshold
• Promotes urinary glucose excretion
• Lowers blood glucose levels independent of insulin action

Currently Available SGLT2 Inhibitors:

1. Dapagliflozin

   • Chemical structure: D-glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, (1S)-, compounded with propanediol hydrate 2
   • Highly selective for SGLT2 receptors 1

2. Empagliflozin

   • Chemical structure: D-Glucitol,1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-, (1S) 3
   • Highly selective for SGLT2 receptors 1
   • Only SGLT2 inhibitor specifically FDA-approved to reduce cardiovascular death risk in adults with T2DM and established cardiovascular disease 1

3. Canagliflozin

   • Has greater potential for inhibiting SGLT1 receptors in addition to SGLT2 1
   • May inhibit intestinal glucose absorption due to SGLT1 inhibition 1

4. Ertugliflozin

   • Highly selective for SGLT2 receptors 1, 4
   • Reduces cardiovascular outcomes and related mortality 1

5. Sotagliflozin

   • Referred to as a "dual SGLT1/SGLT2 inhibitor" due to having the most affinity to SGLT1 receptors 1

Clinical Benefits of SGLT2 Inhibitors

These medications offer several benefits beyond glucose control:

• Glycemic control: Reduce HbA1c levels by approximately 0.5% to 1.0% 1
• Weight reduction: Reduce body weight by 1.5 to 3.5 kg 1
• Blood pressure: Lower systolic blood pressure by 3 to 5 mmHg 1
• Cardiovascular benefits: Reduce the risk of major cardiovascular adverse events, particularly heart failure hospitalization 1
• Renal protection: Reduce renal events and progression of chronic kidney disease 1, 5

Safety Considerations

When prescribing SGLT2 inhibitors, be aware of these potential adverse effects:

• Genitourinary tract infections: Most common adverse effect 1
• Volume depletion: Dose should be reduced in patients with moderate renal impairment 1
• Rare but serious adverse events:
  • Diabetic ketoacidosis
  • Acute kidney injury
  • Bone fracture
  • Toe amputation (particularly with canagliflozin) 1
  • Necrotizing fasciitis of the perineum (Fournier's gangrene) 2

Dosing Considerations

• SGLT2 inhibitors should be discontinued in severe renal impairment 1
• They have a low risk of hypoglycemia when used alone, but risk increases when combined with insulin or insulin secretagogues 1, 2

SGLT2 inhibitors represent an important class of medications for type 2 diabetes management with proven benefits beyond glucose control, particularly for patients with established cardiovascular disease or high cardiovascular risk.