Dapagliflozin: Mechanism, Uses, Side Effects, Contraindications, and Dosage

Dapagliflozin is an oral antidiabetic drug belonging to the sodium-glucose cotransporter-2 (SGLT2) inhibitors class. It is widely used for managing type 2 diabetes mellitus (T2DM) and has additional cardiovascular and renal benefits.

Mechanism of Action

Dapagliflozin works by selectively inhibiting the SGLT2 protein in the proximal renal tubules. SGLT2 is responsible for reabsorbing glucose from the filtrate back into the bloodstream. By blocking SGLT2, dapagliflozin reduces glucose reabsorption, leading to increased urinary glucose excretion and a subsequent reduction in blood glucose levels.

Additionally, it promotes osmotic diuresis, leading to a reduction in blood pressure and body weight. This mechanism also provides cardiovascular and renal protective effects.

Uses of Dapagliflozin

Dapagliflozin is primarily indicated for:

Type 2 Diabetes Mellitus (T2DM): Helps improve glycemic control in adults when combined with diet and exercise.
Heart Failure with Reduced Ejection Fraction (HFrEF): Reduces the risk of cardiovascular death and hospitalization in heart failure patients.
Chronic Kidney Disease (CKD): Slows down disease progression and reduces the risk of kidney failure in patients with CKD.

Side Effects

While dapagliflozin is generally well-tolerated, some common and serious side effects include:

Common Side Effects:
- Urinary tract infections (UTIs)
- Genital fungal infections
- Increased urination
- Dehydration and dizziness
- Hypotension
Serious Side Effects:
- Ketoacidosis (even with normal blood sugar levels)
- Fournier’s gangrene (a rare but serious genital infection)
- Acute kidney injury
- Hypoglycemia (especially when combined with insulin or sulfonylureas)

Contraindications

Dapagliflozin is contraindicated in the following conditions:

Type 1 Diabetes Mellitus: Increases the risk of diabetic ketoacidosis (DKA).
Severe Renal Impairment (eGFR < 25 mL/min/1.73m²): Reduced efficacy and increased risk of adverse effects.
Hypersensitivity to dapagliflozin or any excipients.
Active bladder cancer: Some studies suggest a potential risk.
Pregnancy and Lactation: Safety has not been well established.

Dosage and Administration

For Type 2 Diabetes Mellitus:
- Initial dose: 5 mg once daily in the morning, with or without food.
- If tolerated and additional glycemic control is needed, the dose can be increased to 10 mg once daily.
For Heart Failure (HFrEF) and Chronic Kidney Disease (CKD):
- Recommended dose: 10 mg once daily.
Renal Function Adjustment:
- Not recommended for use in patients with an eGFR below 25 mL/min/1.73m².

Conclusion

Dapagliflozin is a highly effective medication for managing type 2 diabetes, heart failure, and chronic kidney disease. However, it should be used with caution in patients with renal impairment, dehydration risks, or a history of genital infections. Proper monitoring and adherence to the prescribed dosage can maximize benefits while minimizing risks.