dapagliflozin
Brand: Farxiga
Prototype: empagliflozin
Drug Class: SGLT-2 inhibitor
Drug Family: antidiabetic
Subclass: sodium-glucose cotransporter-2 inhibitor
Organ Systems: endocrinecardiovascularrenal
Mechanism of Action
Inhibits SGLT-2 in the renal proximal tubule, blocking reabsorption of filtered glucose, resulting in glycosuria that lowers blood glucose. Additional effects include natriuresis, osmotic diuresis, weight reduction, blood pressure lowering, and hemodynamic effects that reduce cardiovascular and renal stress.
SGLT-2 (sodium-glucose cotransporter 2) in proximal tubule
Indications
- type 2 diabetes mellitus
- heart failure with reduced ejection fraction (HFrEF)
- heart failure with preserved ejection fraction (HFpEF)
- chronic kidney disease (CKD) with albuminuria
Contraindications
- type 1 diabetes
- DKA
- severe renal impairment (eGFR <25 mL/min for T2DM indication)
- dialysis
Adverse Effects
Common
- genital mycotic infections
- urinary tract infections
- polyuria
- volume depletion
Serious
- diabetic ketoacidosis (DKA — euglycemic)
- Fournier's gangrene (necrotizing fasciitis of perineum)
- acute kidney injury (volume depletion)
- lower limb amputation (class effect — less consistent data for dapagliflozin vs. canagliflozin)
Pharmacokinetics (ADME)
| Absorption | oral; bioavailability ~78% |
| Distribution | 91% protein bound |
| Metabolism | hepatic via UGT1A9 (primary glucuronidation) and CYP3A4 (minor) |
| Excretion | renal (75%) and fecal (21%) |
| Half-life | 12.9 hours |
| Onset | rapid |
| Peak | 2 hours |
| Duration | 24 hours |
| Protein Binding | 91% |
| Vd | 118 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| diuretics | additive volume depletion and dehydration risk | moderate |
| insulin or insulin secretagogues | additive hypoglycemia risk; consider dose reduction | moderate |
Nursing Considerations
- Monitor eGFR at baseline and periodically; do not initiate for T2DM if eGFR <45 mL/min; continue for cardiorenal indications until dialysis.
- Educate patients about genital hygiene to prevent mycotic infections; genital candidiasis is the most common side effect.
- Counsel patients (especially those on insulin) about euglycemic DKA: DKA may occur even with normal blood glucose; report nausea, vomiting, malaise.
- Hold dapagliflozin 3–4 days before major surgery, prolonged fasting, or severe illness to prevent euglycemic DKA.
Clinical Pearls
- Dapagliflozin is the first SGLT-2 inhibitor approved for both HFrEF AND HFpEF, expanding its use to all heart failure phenotypes regardless of ejection fraction.
- The cardiorenal benefits of SGLT-2 inhibitors appear to be independent of glucose-lowering, operating through hemodynamic, anti-inflammatory, and direct renal tubular effects.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
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