What is the use of Dapagliflozin (Forxiga)?

From the Guidelines

Dapagliflozin is recommended as a first-line treatment for patients with type 2 diabetes and established heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) to reduce the risk of worsening heart failure and cardiovascular death. The medication works by preventing glucose reabsorption in the kidneys, causing excess glucose to be excreted in urine, which lowers blood sugar levels. Beyond glucose control, it offers cardiovascular benefits by reducing heart failure hospitalizations and mortality, and renal protection by slowing kidney function decline 1.

Key Benefits and Considerations

• The typical starting dose is 10 mg taken once daily in the morning, with or without food, and this dose is also recommended for heart failure patients with reduced ejection fraction.
• Common side effects include genital yeast infections, urinary tract infections, and volume depletion.
• Patients should maintain adequate hydration while taking this medication and temporarily stop it during periods of reduced oral intake or illness that may cause dehydration.
• Blood pressure and kidney function should be monitored regularly, and patients should be vigilant for signs of diabetic ketoacidosis, a rare but serious side effect.
• The use of SGLT inhibitors increases the susceptibility to diabetic ketoacidosis, particularly when other risk factors or situations occur, such as insulin pump malfunctions, significant reduction in insulin doses, and nutritional intake plans with prolonged periods of fasting or carbohydrate restriction 1.

Clinical Evidence

• The DAPA-HF trial demonstrated that dapagliflozin treatment had a lower risk of the primary outcome of a composite of worsening heart failure or cardiovascular death (HR 0.74 [95% CI 0.65–0.85]) compared with placebo 1.
• The EMPEROR-Reduced and EMPEROR-Preserved trials also showed significant reductions in cardiovascular death or hospitalization for heart failure with empagliflozin treatment 1.
• A large recent meta-analysis of data from EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and the SOLOIST-WHF trial included 21,947 individuals and demonstrated reduced risk for the composite of cardiovascular death or hospitalization for heart failure with SGLT2 inhibitor use 1.

Recommendations

• Dapagliflozin should be considered for all patients with type 2 diabetes and established heart failure, regardless of ejection fraction, to reduce the risk of worsening heart failure and cardiovascular death.
• Patients should be educated on the signs and symptoms of diabetic ketoacidosis and the importance of maintaining adequate hydration while taking this medication.
• Regular monitoring of blood pressure and kidney function is essential to minimize the risk of adverse effects.

From the FDA Drug Label

DAPAGLIFLOZIN TABLETS are a prescription medicine used: ∘ to reduce the risk of further worsening of your kidney disease, end-stage kidney disease (ESKD), death due to cardiovascular disease, and hospitalization for heart failure in adults with chronic kidney disease ∘ to reduce the risk of cardiovascular death, hospitalization for heart failure and urgent heart failure visit in adults with heart failure, when the heart cannot pump enough blood to the rest of your body ∘ to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes who also have known cardiovascular disease or multiple cardiovascular risk factors ∘ along with diet and exercise to improve blood sugar (glucose) control in adults and children who are 10 years of age and older with type 2 diabetes

Dapagliflozin is used for several purposes, including:

• Reducing the risk of kidney disease progression and cardiovascular events in adults with chronic kidney disease
• Reducing the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure
• Reducing the risk of hospitalization for heart failure in adults with type 2 diabetes and cardiovascular disease or risk factors
• Improving blood sugar control in adults and children with type 2 diabetes, in combination with diet and exercise 2

From the Research

Dapagliflozin Overview

• Dapagliflozin is a highly potent, reversible, and selective sodium-glucose cotransporter-2 inhibitor indicated for the treatment of type 2 diabetes (T2D) 3.
• It is approved for use as monotherapy and as add-on combination therapy with other glucose-lowering agents, including insulin, for T2D when diet and exercise alone do not provide adequate glycaemic control 3.

Clinical Benefits

• Dapagliflozin provides effective glycaemic control, reduces body weight and blood pressure, and has a low risk of hypoglycaemia 3, 4.
• It reduces the rate of cardiovascular death or hospitalization for heart failure and possibly reduces progression of renal disease relative to placebo in patients with established atherosclerotic cardiovascular disease or multiple risk factors for cardiovascular disease 3, 5.
• Dapagliflozin has been shown to reduce the risk of hospitalization for heart failure, cardiovascular death, and renal disease in patients with heart failure with reduced ejection fraction, regardless of the presence or absence of diabetes 4, 5, 6.

Safety Profile

• Dapagliflozin is generally well tolerated, with a low risk of hypoglycaemia, but may increase the risk of genital infections, urinary tract infections, and diabetic ketoacidosis 3, 4, 7.
• The most common adverse effects of dapagliflozin include genital infections, urinary tract infections, and increased risk of Fournier's gangrene 6, 7.

Clinical Trials

• numerous clinical trials, including the DECLARE-TIMI 58 study, DAPA-HF trial, and DAPA-CKD trial, have demonstrated the efficacy and safety of dapagliflozin in patients with T2D, heart failure, and chronic kidney disease 4, 5.
• Ongoing trials, such as the DELIVER, DAPA-ACT HF-TIMI 68, and DICTATE-AHF studies, will provide further insight into the effects of dapagliflozin in various clinical scenarios 4.