From the Guidelines
Dapagliflozin is recommended for patients with type 2 diabetes and heart failure, with a starting dose of 10 mg once daily, as it has been shown to reduce the risk of hospitalization for heart failure and cardiovascular death, as well as provide renal protection in at-risk patients 1.
Key Considerations
- When initiating dapagliflozin, healthcare providers should assess kidney function, as it's not recommended for patients with eGFR below 25 mL/min/1.73m² 1.
- Common side effects include genital mycotic infections and increased urination, and patients should be monitored for volume depletion, especially those on diuretics or with low blood pressure 1.
- Dapagliflozin carries a risk of diabetic ketoacidosis (DKA), even with normal blood glucose levels, so it should be temporarily discontinued during acute illness or surgical procedures 1.
Mechanism of Action
- The medication works by inhibiting sodium-glucose cotransporter-2 in the kidneys, causing glucose excretion in urine, which lowers blood glucose and provides cardiovascular benefits through multiple mechanisms 1.
Cardiovascular and Renal Protection
- Beyond glucose control, dapagliflozin offers significant cardiovascular protection, reducing hospitalization for heart failure and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), even in non-diabetic patients 1.
- It also provides renal protection by reducing the progression of kidney disease in at-risk patients 1.
Special Populations
- Dapagliflozin should not be used during pregnancy or breastfeeding, and caution is needed in elderly patients due to increased risk of volume depletion and urinary tract infections 1.
From the FDA Drug Label
DAPAGLIFLOZIN tablets, for oral use
INDICATIONS AND USAGE DAPAGLIFLOZIN TABLETS a sodium-glucose cotransporter 2 (SGLT2) inhibitor, are indicated: • To reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression (1) • To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. (1) • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors (1) • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. (1)
DOSAGE AND ADMINISTRATION • Assess renal function prior to initiation and then as clinically indicated. Assess volume status and correct volume depletion before initiating. (2. 1) • To improve glycemic control, the recommended starting dosage is 5 mg orally once daily. Dosage can be increased to 10 mg orally once daily for additional glycemic control. (2.2) • For all other indications, the recommended dosage is 10 mg orally once daily. (2.3)
The considerations and guidelines for using Dapagliflozin in patients with type 2 diabetes or heart failure include:
- Assessing renal function prior to initiation and as clinically indicated
- Assessing volume status and correcting volume depletion before initiating
- Using a recommended starting dosage of 5 mg orally once daily to improve glycemic control, with the option to increase to 10 mg orally once daily for additional control
- Using a recommended dosage of 10 mg orally once daily for all other indications, including reducing the risk of hospitalization for heart failure and cardiovascular death
- Withholding Dapagliflozin for at least 3 days prior to major surgery or procedures associated with prolonged fasting 2
- Monitoring patients for ketoacidosis and discontinuing Dapagliflozin if suspected, regardless of presenting blood glucose levels 2
From the Research
Considerations for Using Dapagliflozin
- Dapagliflozin is a selective and reversible inhibitor of sodium-glucose linked transporter type 2 (SGLT2), which reduces glucose reabsorption and decreases serum glucose concentration in an insulin-independent manner 3.
- The drug is approved as monotherapy in patients with type 2 diabetes mellitus (T2DM) who cannot tolerate metformin or in combination with other antidiabetic drugs, with the exception of pioglitazone due to the theoretical increased risk of bladder cancer 3.
- Dapagliflozin should not be prescribed in patients with moderate or severe renal impairment or in patients at risk for developing volume depletion 3, 4.
- The drug is associated with increased incidence of genital and lower urinary tract infections, but these infections are usually mild to moderate and respond to standard antimicrobial treatment 3, 5.
Guidelines for Patients with Type 2 Diabetes
- Dapagliflozin reduces renal glucose reabsorption by inhibiting the transporter protein SGLT2 in the renal proximal tubule, thereby increasing urinary glucose excretion and reducing blood glucose levels 4.
- The mechanism of action is independent of insulin secretion or action, making dapagliflozin a useful treatment option in combination with other antihyperglycaemic drugs 4.
- Clinical trials have demonstrated reductions in glycosylated haemoglobin, fasting plasma glucose levels, and bodyweight with dapagliflozin treatment 4, 6.
- Dapagliflozin has a low risk of hypoglycaemia, although the incidence varies depending on background therapy 4, 7.
Guidelines for Patients with Heart Failure
- There is no direct evidence in the provided studies regarding the use of dapagliflozin in patients with heart failure.
- However, dapagliflozin has been shown to reduce blood pressure levels through weight loss and its action as an osmotic diuretic, which may be beneficial in patients with heart failure 3.
- Further research is needed to evaluate the effects of dapagliflozin on cardiovascular outcomes in patients with heart failure 3, 6.