Examples of SGLT2 Inhibitors
Empagliflozin, canagliflozin, and dapagliflozin are the primary examples of SGLT2 inhibitors used in clinical practice for the treatment of type 2 diabetes. 1, 2, 3
Mechanism of Action
SGLT2 inhibitors work by:
- Inhibiting sodium-glucose cotransporter 2 (SGLT2) proteins in the proximal tubule of the kidney
- Reducing renal glucose reabsorption and increasing urinary glucose excretion
- Lowering blood glucose through an insulin-independent mechanism 3
The primary site of action is the proximal convoluted tubule in the kidneys, where SGLT2 is responsible for approximately 90% of glucose reabsorption from the glomerular filtrate back into circulation 1, 2.
Available SGLT2 Inhibitors
| SGLT2 Inhibitor | Selectivity | Key Features |
|---|---|---|
| Empagliflozin | High | FDA-approved to reduce CV death [1] |
| Dapagliflozin | High | Available in 5mg and 10mg tablets [4] |
| Canagliflozin | Low | First-in-class SGLT2 inhibitor approved in US [5] |
| Ertugliflozin | High | Newer agent with CV benefits [2] |
Clinical Benefits
SGLT2 inhibitors provide multiple benefits beyond glycemic control:
Cardiovascular benefits: Reduced risk of major adverse cardiovascular events (MACE)
Heart failure benefits: 26-35% reduction in hospitalization for heart failure 1, 2
Renal protection: Slowed progression of chronic kidney disease and reduced albuminuria 2
Additional benefits:
- Weight loss through caloric loss via glucosuria
- Blood pressure reduction
- Low risk of hypoglycemia when used as monotherapy 6
Clinical Considerations
When prescribing SGLT2 inhibitors:
Dosing: Most are administered once daily (e.g., empagliflozin 10-25mg, dapagliflozin 5-10mg, canagliflozin 100-300mg) 2, 3, 4
Renal function: Efficacy is reduced in patients with impaired renal function; specific eGFR cutoffs vary by agent 2
Potential side effects:
Medication adjustments: When initiating SGLT2 inhibitors, consider reducing sulfonylurea dose by 50% or basal insulin dose by 20% to prevent hypoglycemia 2
Clinical Pearls
- SGLT2 inhibitors can be taken with or without food 3
- They are generally well-tolerated with a favorable safety profile 5, 6
- The cardiovascular and renal benefits appear to be class effects, though empagliflozin is the only agent specifically FDA-approved for reducing cardiovascular death 1
- SGLT2 inhibitors are particularly beneficial for patients with established cardiovascular disease, heart failure, or chronic kidney disease 1, 2
SGLT2 inhibitors represent an important therapeutic class for type 2 diabetes management, offering benefits beyond glycemic control that can significantly impact morbidity and mortality outcomes.