Dapagliflozin: A Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
Dapagliflozin is a highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that works by blocking glucose reabsorption in the proximal renal tubules, thereby increasing urinary glucose excretion and reducing blood glucose levels. 1
Mechanism of Action
Dapagliflozin specifically targets and inhibits SGLT2, which is responsible for the majority of glucose reabsorption in the kidneys. By inhibiting this transporter:
- It prevents reabsorption of filtered glucose from the tubular lumen
- It promotes urinary glucose excretion (glucosuria)
- It reduces sodium reabsorption and increases sodium delivery to the distal tubule 1
- It functions through an insulin-independent mechanism 2
This unique mechanism distinguishes SGLT2 inhibitors from other antidiabetic medications as it does not depend on pancreatic β-cell function or insulin sensitivity modulation 2.
Classification Details
Dapagliflozin belongs to a distinct class of medications with specific characteristics:
- Primary classification: Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor 3, 1
- Selectivity: High selectivity for SGLT2 receptors (compared to other transporters like SGLT1) 4
- Chemical structure: Described chemically as D-glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, (1S)-, compounded with (2S)-1,2-propanediol, hydrate (1:1:1) 1
Clinical Applications
While primarily developed for glycemic control in type 2 diabetes, dapagliflozin has demonstrated significant benefits beyond glucose lowering:
- Glycemic control: Reduces HbA1c by approximately 0.5-1.0% 4, 2
- Cardiovascular benefits: Reduces risk of hospitalization for heart failure and cardiovascular death 3
- Renal protection: Slows progression of chronic kidney disease 3, 4
- Additional benefits: Promotes weight reduction (1.5-3.5 kg) and lowers systolic blood pressure (3-5 mmHg) 4, 5
Comparison to Other SGLT2 Inhibitors
Dapagliflozin is one of several SGLT2 inhibitors, with each having specific characteristics:
- Highly selective SGLT2 inhibitors: Dapagliflozin, empagliflozin, ertugliflozin 4
- Less selective: Canagliflozin (has some SGLT1 inhibition) 4
- Dual action: Sotagliflozin (inhibits both SGLT1 and SGLT2) 3
Safety Considerations
Key safety considerations when using dapagliflozin include:
- Common adverse effects: Genital infections (2-13%) and urinary tract infections (more common than with placebo) 6, 5
- Hypoglycemia risk: Low risk when used as monotherapy (similar to placebo) 6, 5
- Renal considerations: Not recommended for glycemic control when eGFR <45 mL/min/1.73 m² 1
- Rare but serious effects: Euglycemic ketoacidosis, acute kidney injury 4
Dapagliflozin represents an important advancement in diabetes management, offering benefits beyond glycemic control through its unique mechanism of action as an SGLT2 inhibitor.