What are the indications and dosing guidelines for dapagliflozin (SGLT2 inhibitor) in patients with type 2 diabetes and heart failure?

From the Guidelines

Dapagliflozin is indicated for adults with type 2 diabetes mellitus (T2DM) to improve glycemic control and for adults with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization, regardless of diabetes status, at a standard dose of 10 mg once daily. The dose of dapagliflozin should not be titrated for cardiovascular or renal risk reduction, as there is no evidence of a graded dose response regarding these effects 1. For patients with T2DM, dapagliflozin can be used as monotherapy or as add-on therapy with other antidiabetic medications. For heart failure patients, the 10 mg daily dose is recommended regardless of renal function, though it should not be initiated in patients with eGFR less than 25 mL/min/1.73m² 1. Before starting dapagliflozin, assess volume status and correct any volume depletion. Monitor renal function, especially during initiation and in situations that may lead to reduced renal function. Patients should be advised about potential side effects including genital mycotic infections, urinary tract infections, and volume depletion. Dapagliflozin works by inhibiting sodium-glucose cotransporter 2 in the kidneys, promoting urinary glucose excretion, which reduces blood glucose levels while also providing cardiovascular and renal benefits through mechanisms including improved cardiac energetics, reduced cardiac fibrosis, and decreased cardiac preload and afterload. Key considerations for the use of dapagliflozin in patients with T2DM and heart failure include:

• The drug's ability to reduce the risk of hospitalization for heart failure and cardiovascular death in patients with HFrEF, as demonstrated in the DAPA-HF trial 1.
• The importance of monitoring renal function and adjusting the dose accordingly, as the drug is not recommended for use in patients with eGFR less than 25 mL/min/1.73m² 1.
• The potential for dapagliflozin to increase the risk of diabetic ketoacidosis, particularly in patients with type 1 diabetes or those who are prone to ketoacidosis 1. Some of the benefits of using dapagliflozin in patients with T2DM and heart failure include:
• Reduced risk of cardiovascular death and hospitalization for heart failure
• Improved glycemic control
• Potential for improved renal outcomes, including reduced risk of kidney failure and doubling of serum creatinine
• Convenient once-daily dosing regimen. However, it is essential to weigh these benefits against the potential risks and consider alternative treatment options for patients who may not be suitable candidates for dapagliflozin therapy. In clinical practice, dapagliflozin can be used in a variety of settings, including:
• As initial therapy for patients with T2DM who are at high risk of cardiovascular events
• As add-on therapy for patients with T2DM who are already receiving other antidiabetic medications
• For patients with HFrEF who are at risk of hospitalization for heart failure or cardiovascular death. Overall, dapagliflozin is a valuable treatment option for patients with T2DM and heart failure, offering a range of benefits that can help improve outcomes and reduce the risk of cardiovascular events.

From the FDA Drug Label

Dapagliflozin and Metformin HCl extended-release tablets are a combination of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and metformin hydrochloride (HCl), a biguanide, indicated 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 Dapagliflozin when used as a component of Dapagliflozin and Metformin HCl extended-release tablets is indicated in adults with type 2 diabetes mellitus to reduce the risk of: • Sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in patients with chronic kidney disease at risk of progression • Cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in patients with heart failure • Hospitalization for heart failure in patients with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors To improve glycemic control, for patients aged 10 years and older not already taking dapagliflozin, the recommended starting dosage for dapagliflozin is 5 mg once daily For indications in adults related to heart failure and chronic kidney disease the recommended dosage of dapagliflozin is 10 mg once daily

The indications for dapagliflozin in patients with type 2 diabetes and heart failure include:

• Reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in patients with heart failure
• Reducing the risk of hospitalization for heart failure in patients with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors The dosing guidelines for dapagliflozin in these patients are:
• 10 mg once daily for adults with type 2 diabetes mellitus to reduce the risk of heart failure and chronic kidney disease 2 2

From the Research

Indications for Dapagliflozin

• Dapagliflozin is indicated for the treatment of patients with type 2 diabetes mellitus (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) or heart failure 3.
• It is also indicated for the treatment of patients with heart failure with reduced ejection fraction (HFrEF), with or without diabetes 4.
• Additionally, dapagliflozin has been shown to be effective in patients with heart failure and a mildly reduced or preserved ejection fraction 5.

Dosing Guidelines

• The recommended dose of dapagliflozin is 10 mg once daily, taken orally 4, 5.
• The dose should be taken in the morning, with or without food 6.
• No dose adjustment is necessary for patients with mild or moderate renal impairment, but the dose should be adjusted for patients with severe renal impairment 6.

Efficacy in Patients with Type 2 Diabetes and Heart Failure

• Dapagliflozin has been shown to reduce the risk of worsening heart failure and cardiovascular death in patients with T2DM and heart failure 3, 6.
• It has also been shown to reduce the risk of hospitalization for heart failure and cardiovascular death in patients with heart failure and a reduced ejection fraction, with or without diabetes 4.
• In patients with heart failure and a mildly reduced or preserved ejection fraction, dapagliflozin has been shown to reduce the combined risk of worsening heart failure and cardiovascular death 5.

Safety and Tolerability

• Dapagliflozin has been shown to be generally well-tolerated, with a safety profile similar to that of placebo 4, 6.
• Common adverse events include volume depletion, kidney adverse events, and genital infections 4, 6.
• Dapagliflozin has also been associated with an increased risk of diabetic ketoacidosis, particularly in patients with type 1 diabetes 6.