From the Guidelines
Dapagliflozin is recommended as a first-line treatment for patients with type 2 diabetes and established heart failure or chronic kidney disease, due to its proven benefits in reducing the risk of worsening heart failure, cardiovascular death, and kidney disease progression, as demonstrated in the DAPA-HF trial 1 and the CREDENCE trial 1.
Key Points
- The typical starting dose of dapagliflozin is 10 mg taken once daily in the morning, with or without food.
- For heart failure patients, the dose is 10 mg daily regardless of kidney function, while for diabetes, dose adjustments may be needed for those with reduced kidney function.
- Common side effects include genital yeast infections, urinary tract infections, and increased urination.
- Patients should maintain adequate hydration while taking dapagliflozin and temporarily stop the medication during periods of reduced oral intake or illness that may cause dehydration.
Mechanism of Action
- Dapagliflozin works by preventing glucose reabsorption in the kidneys, causing excess glucose to be excreted in urine, which lowers blood sugar levels.
- This mechanism also provides cardiovascular and kidney benefits by reducing blood pressure, decreasing fluid overload, and improving heart function.
Monitoring and Precautions
- Patients should monitor for rare but serious side effects like diabetic ketoacidosis, especially during illness or fasting, and should seek immediate medical attention if experiencing symptoms such as nausea, vomiting, abdominal pain, or unusual fatigue.
- The drug should be used with caution in patients with prior amputation, severe peripheral neuropathy, severe peripheral vascular disease, or active diabetic foot ulcers or soft tissue infections.
Evidence-Based Recommendations
- The DAPA-HF trial 1 demonstrated a 26% reduction in the risk of worsening heart failure or cardiovascular death in patients with heart failure with reduced ejection fraction.
- The CREDENCE trial 1 showed a 39% reduction in the risk of hospitalization for heart failure and a 31% reduction in the composite of cardiovascular death or hospitalization for heart failure in patients with diabetic kidney disease.
- The EMPEROR-Reduced trial 1 demonstrated a 21% reduction in the risk of cardiovascular death or hospitalization for worsening heart failure in patients with heart failure with reduced ejection fraction.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Dapagliflozin Overview
- Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor indicated for the treatment of type 2 diabetes and heart failure with reduced ejection fraction 2, 3, 4.
- It has been shown to provide effective glycaemic control, reduce body weight and blood pressure, and have cardioprotective and renoprotective properties 2, 5, 6.
Clinical Benefits
- Dapagliflozin has been found to reduce the risk of cardiovascular death or hospitalization for heart failure in patients with type 2 diabetes and established atherosclerotic cardiovascular disease or multiple risk factors 2, 6.
- It has also been shown to reduce the risk of worsening heart failure or cardiovascular death in patients with heart failure with reduced ejection fraction, regardless of the presence or absence of type 2 diabetes 3, 4.
- The benefits of dapagliflozin have been found to be consistent across different patient populations, including those with and without background use of cardiovascular medications 5.
Safety Profile
- Dapagliflozin has been found to be generally well-tolerated, with a low risk of hypoglycaemia and a safety profile consistent with its known safety profile in other indications 2, 3, 5.
- The most common adverse events associated with dapagliflozin include genital infections and diabetic ketoacidosis, although these are rare 2.
- There have been no significant treatment interactions with concomitant cardiovascular medications for key safety events, such as volume depletion, acute kidney injury, or hyperkalemia 5.