dapagliflozin

SGLT2 inhibitor· Brands: Forxiga, Farxiga, OxraPO

Mechanism of action

Dapagliflozin selectively inhibits sodium-glucose cotransporter 2 in the proximal renal tubule, reducing renal glucose reabsorption and increasing urinary glucose excretion. This lowers blood glucose independently of insulin. It also reduces sodium reabsorption, causing natriuresis and osmotic diuresis, which contributes to blood pressure reduction and fluid volume status.

Pharmacokinetics

Dapagliflozin is rapidly absorbed after oral administration, with no clinically relevant effect of food. It is extensively metabolised via UDP-glucuronosyltransferase 1A9 to inactive metabolites; only a small amount is excreted unchanged. The plasma half-life is about 12.9 hours, allowing once-daily dosing. Protein binding is ~91%. It primarily undergoes renal excretion as metabolites, and hepatic impairment may increase exposure.

Indications & dosing

Type 2 diabetes mellitus

Adjunct to diet and exercise. May be used alone or in combination with other antidiabetic agents. Renal function should be assessed before initiation.

adult · PO: 10 mg once daily · Adjunct to diet and exercise. May be used alone or in combination with other antidiabetic agents. Renal function should be assessed before initiation.

Heart failure (reduced ejection fraction)

To reduce the risk of cardiovascular death and hospitalization for heart failure. Not for relief of acute heart failure.

adult · PO: 10 mg once daily · To reduce the risk of cardiovascular death and hospitalization for heart failure. Not for relief of acute heart failure.

Chronic kidney disease

To slow progression of kidney disease in adults with eGFR 25-75 mL/min/1.73m². Initiation not recommended if eGFR < 25.

adult · PO: 10 mg once daily · To slow progression of kidney disease in adults with eGFR 25-75 mL/min/1.73m². Initiation not recommended if eGFR < 25.

Contraindications & precautions

Hypersensitivity to dapagliflozin or any excipient · Avoid in known hypersensitivity.
Diabetic ketoacidosis (DKA) · Do not use in patients with DKA; risk of euglycaemic DKA.
Severe renal impairment (eGFR < 25 mL/min/1.73 m²) or end-stage renal disease (ESRD) on dialysis · No glycaemic benefit; risk of volume depletion.
Type 1 diabetes · Not approved for Type 1 DM; increased risk of DKA.
Assess renal function before starting and monitor regularly; avoid in severe renal impairment.
Correct volume depletion before initiation; monitor for hypotension in at-risk patients.
Advise on sick-day rules: temporarily stop during acute illness, fasting, or poor oral intake.
Counsel patients on signs of DKA (nausea, vomiting, abdominal pain) and advise to check ketones if symptomatic, even with normal blood glucose.
Use caution when combining with insulin or sulfonylureas; consider dose reduction to prevent hypoglycaemia.
Maintain good hygiene and hydration to reduce risk of genital and urinary infections.

Adverse effects

Genital mycotic infection
Urinary tract infection
Polyuria (increased urination)
Volume depletion (hypotension, dizziness)
Hypoglycaemia (when used with insulin or sulfonylureas)
Diabetic ketoacidosis (can occur with normal glucose)serious
Fournier's gangrene (necrotising fasciitis of perineum)serious
Bone fracture (increased risk)

Renal & hepatic adjustment

eGFR 45+: No dose adjustment required.
eGFR 30–44: No dose adjustment required; may be less effective for glycaemic control. Continue if already on therapy for heart failure or chronic kidney disease.
eGFR 25–29: Not recommended for glycaemic control. May be initiated for heart failure or chronic kidney disease if eGFR is 25-29 mL/min/1.73m², but not for glucose lowering. (avoid)
eGFR 0–25: Avoid in patients with eGFR <25 mL/min/1.73m², or on dialysis. (avoid)

Monitoring, pregnancy & toxicity

eGFR/creatinine · At baseline, then at least annually; more frequently if renal function declines
Blood pressure · At baseline and periodically, especially if dehydrated or at risk of hypotension
Fluid status · Assess for signs of dehydration or volume depletion
Blood ketones · If symptoms of ketoacidosis occur, check ketones even if glucose is normal
Urinary and genital symptoms · Monitor for signs of genitourinary infection
Blood glucose (if used for diabetes) · Regularly as part of diabetes management
Pregnancy: Not recommended during pregnancy, particularly in the second and third trimester; discontinue when pregnancy is detected.
Toxicity: Volume depletion and hypotension due to osmotic diuresis · Administer fluids to restore intravascular volume; monitor blood pressure and electrolytes.
Toxicity: Euvolaemic or ketoacidosis (rare) · Euglycaemic diabetic ketoacidosis (rare)
Toxicity: Hypoglycaemia (unlikely as monotherapy, but possible in combination with insulin or sulfonylureas) · Give oral glucose if conscious, or intravenous dextrose if severe; adjust concomitant glucose-lowering therapy.
Toxicity: Genitourinary infections (candidiasis, urinary tract infection) · Treat with appropriate antifungal or antibacterial therapy; consider discontinuing if severe or recurrent.

Clinical notes

Dapagliflozin is indicated for type 2 diabetes, heart failure, and chronic kidney disease, with benefits on cardiovascular and renal outcomes. It is used as monotherapy or in combination with other antidiabetic agents, and also for heart failure irrespective of diabetes status. Monitor for genital mycotic infections and euglycemic diabetic ketoacidosis; ensure adequate hydration. Dose adjustment is not required for mild renal impairment, but use is not recommended when eGFR is below 25 ml/min/1.73 m² for diabetes; however, it is used in CKD with eGFR ≥20 for the renal indications. It may cause hypotension. Seek specialist advice for use in pregnancy and breastfeeding.

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BNF; local formulary