Dapagliflozin tablets for reducing risks in chronic kidney disease, heart failure, and type 2 diabetes

Dapagliflozin is an oral medication in tablet form used primarily to manage blood sugar levels in adults and children aged 10 years and older with type 2 diabetes mellitus. Additionally, it helps reduce risks associated with chronic kidney disease and heart failure by lowering the chances of kidney failure, cardiovascular death, and hospitalizations for heart failure. The medication works as part of diet and exercise regimens to improve glycemic control.

Dapagliflozin is approved for the following uses in adults, and in pediatric patients aged 10 years and older for glycemic control:

• To improve glycemic control as an adjunct to diet and exercise in type 2 diabetes mellitus.
• To reduce the risk of sustained decline in kidney function, progression to end-stage kidney disease, cardiovascular death, and heart failure hospitalizations in adults with chronic kidney disease at risk of progression.
• To decrease the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure.
• To lower the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.

Limitations: It is not recommended for glycemic control in type 1 diabetes mellitus, nor for use in type 2 diabetes patients with severe kidney impairment (eGFR less than 45 mL/min/1.73 m2). It is not expected to be effective in patients with polycystic kidney disease or those requiring immunosuppressive therapy for kidney disease.

dapagliflozin

Dapagliflozin belongs to a class of drugs called sodium-glucose cotransporter 2 (SGLT2) inhibitors. It lowers blood sugar by helping the kidneys remove excess glucose through urine. This action also helps reduce strain on the heart and kidneys, decreasing risks of worsening kidney function, heart failure events, and cardiovascular death.

Before starting dapagliflozin, kidney function and volume status should be assessed and any volume depletion corrected.

• For glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes, start at 5 mg orally once daily, which may be increased to 10 mg once daily if needed.
• For reducing risks related to kidney disease, heart failure, or cardiovascular events in adults, the recommended dose is 10 mg orally once daily.
• For patients with type 2 diabetes and eGFR ≥45 mL/min/1.73 m2, dosing is as above. It is not recommended in patients with eGFR 2 for glycemic control due to likely ineffectiveness.
• In patients with chronic kidney disease treated for risk reduction (non-glycemic control indications), dapagliflozin can be started if eGFR ≥25 mL/min/1.73 m2. Initiation under 25 mL/min/1.73 m2 is not recommended, but treatment may continue if eGFR declines below this while on therapy.
• Dapagliflozin should be withheld for at least 3 days before surgery or procedures involving prolonged fasting and resumed after clinical stability and oral intake return.
• If a dose is missed, take it as soon as possible and do not double the next dose.

Dapagliflozin is contraindicated in patients with a history of serious hypersensitivity to dapagliflozin or any excipients, including anaphylaxis and angioedema.

It is contraindicated in patients with type 2 diabetes who have an eGFR below 30 mL/min/1.73 m2 or end-stage renal disease.

It is also contraindicated in patients with acute or chronic metabolic acidosis including diabetic ketoacidosis.

Serious warnings and precautions include:

• Diabetic ketoacidosis (DKA): Dapagliflozin significantly increases the risk of DKA in patients with type 1 diabetes mellitus, a life-threatening condition. It is not approved for use in type 1 diabetes. Ketoacidosis may occur even with normal or mildly elevated blood sugar levels. Monitor for ketoacidosis symptoms and discontinue if suspected.
• Volume depletion: Can cause dehydration, hypotension, and acute kidney injury. Patients at higher risk include the elderly, those with impaired renal function, and those on diuretics. Assess and correct volume status before starting.
• Genitourinary infections: Increased risk of urinary tract infections and genital fungal infections. Rarely, severe infections like Fournier’s gangrene (necrotizing fasciitis of the perineum) occur, requiring urgent medical treatment.
• Hypoglycemia: Risk increases when used with insulin or insulin secretagogues; dose adjustments of these agents may be needed.

Common adverse effects (≥2% incidence) in adults for glycemic control include:

• Female genital mycotic infections (~7-8% of females treated)
• Urinary tract infections (~4-6%)
• Nasopharyngitis (~6%)
• Back pain (~3-4%)
• Increased urination (~3-4%)
• Male genital mycotic infections

Severe but rarer adverse reactions reported include diabetic ketoacidosis, volume depletion events, serious genitourinary infections including urosepsis, pyelonephritis, and necrotizing fasciitis of the perineum.

Dapagliflozin may increase the risk of hypoglycemia when used with insulin or insulin secretagogues such as sulfonylureas. Dose adjustments of these agents should be considered to minimize this risk.