1. Clinical Overview
Dapagliflozin is a potent, selective, and reversible inhibitor of sodium-glucose co-transporter 2 (SGLT2). It is an oral anti-diabetic agent (gliflozin class) used primarily for the management of type 2 diabetes mellitus (T2DM). By inhibiting SGLT2 in the proximal renal tubules, it reduces renal glucose reabsorption, leading to increased urinary glucose excretion (glucosuria) and a consequent reduction in plasma glucose levels. It is also indicated for heart failure and chronic kidney disease, irrespective of diabetes status.
| Onset | Duration | Bioavailability |
|---|---|---|
| The pharmacodynamic effect (increase in urinary glucose excretion) begins within 1 hour of oral administration. | Approximately 24 hours, supporting once-daily dosing. | 78% following oral administration. |
2. Mechanism of Action
Dapagliflozin selectively and competitively inhibits SGLT2, the primary transporter responsible for reabsorbing approximately 90% of filtered glucose from the proximal renal tubule back into the circulation. Inhibition of SGLT2 reduces the renal threshold for glucose (RTG), leading to increased excretion of glucose in the urine (glucosuria). This results in a reduction of plasma glucose concentrations and HbA1c. The caloric loss (approximately 200-300 kcal/day) and osmotic diuresis contribute to weight loss and modest reductions in systolic blood pressure.
3. Indications & Uses
- Type 2 Diabetes Mellitus (as monotherapy or in combination with other glucose-lowering agents including insulin)
- Heart Failure with reduced Ejection Fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization
- Chronic Kidney Disease (CKD) to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization
4. Dosage & Administration
Adult Dosage: Recommended starting dose is 10mg once daily, taken orally in the morning, with or without food. For T2DM, can be initiated at 5mg and increased to 10mg based on efficacy and tolerability. For HF and CKD, the recommended dose is 10mg once daily.
Administration: Tablet should be swallowed whole with a glass of water. Can be taken with or without food, but taking it in the morning is preferred to minimize the risk of nocturia. Patients should maintain adequate fluid intake to prevent volume depletion.
5. Side Effects
Common side effects may include:
- Genital mycotic infections (e.g., vulvovaginal candidiasis, balanitis)
- Urinary tract infections (including cystitis)
- Increased urination
- Dyslipidemia (increased LDL-C and HDL-C)
- Back pain
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Insulin or Insulin Secretagogues (Sulfonylureas, Meglitinides) | Increased risk of hypoglycemia. Dose reduction of insulin/secretagogue may be required. | Major |
| Loop Diuretics (e.g., Furosemide) | Potentiation of diuresis and increased risk of volume depletion and hypotension. | Moderate |
| Other SGLT2 Inhibitors | Concomitant use not recommended due to additive effects and increased risk of adverse reactions. | Major |
| Rifampicin | Decreases systemic exposure of dapagliflozin. May require monitoring of glycemic control. | Moderate |
| Lithium | SGLT2 inhibitors may decrease lithium concentrations. Monitor lithium levels closely. | Moderate |
7. Patient Counselling
- DO take the tablet once daily, preferably in the morning.
- DO maintain adequate fluid intake to prevent dehydration.
- DO monitor your blood glucose levels as advised by your doctor.
- DO inform your doctor about any other medicines you are taking.
- DO practice good personal hygiene, especially genital hygiene, to reduce infection risk.
- DONT stop taking this medicine without consulting your doctor.
- DONT take this medicine if you are pregnant, planning pregnancy, or breastfeeding without discussing with your doctor.
- DONT take a double dose if you miss one. Take the next dose at the usual time.
8. Toxicology & Storage
Overdose: Expected symptoms would be related to its pharmacodynamic effects: severe polyuria, volume depletion, hypotension, dizziness, and possibly hypoglycemia if taken with other anti-diabetic drugs.
Storage: Store at room temperature (15°C to 30°C). Protect from moisture and light. Keep the blister strips in the outer carton. Keep out of reach of children.