Is Dapagliflozin (Forxiga) contraindicated with insulin, loop diuretics, impaired renal function (GFR less than 40), or ketonuria?

From the Guidelines

Dapagliflozin is contraindicated in patients with severe renal impairment (eGFR less than 30 mL/min/1.73m²) but can be used with caution in those with eGFR between 30-45 mL/min/1.73m², and its use with insulin or loop diuretics requires careful consideration of dose adjustments and monitoring for potential adverse effects, such as hypoglycemia, excessive diuresis, and diabetic ketoacidosis (DKA) 1.

Key Considerations

• Dapagliflozin's efficacy and safety in patients with renal impairment have been evaluated, and it is recommended to avoid its use in patients with eGFR less than 30 mL/min/1.73m² for glycemic control 1.
• For patients with eGFR between 30-45 mL/min/1.73m², dapagliflozin can be used at a dose of 10 mg daily, but its initiation is not recommended if eGFR is less than 25 mL/min/1.73m² 1.
• When using dapagliflozin with insulin or loop diuretics, careful monitoring of blood glucose levels, renal function, and volume status is necessary to prevent hypoglycemia, excessive diuresis, and other potential adverse effects 1.
• Patients with ketonuria should be cautious when using dapagliflozin, as SGLT2 inhibitors can increase the risk of DKA, and education on recognizing the symptoms of DKA is essential 1.

Monitoring and Dose Adjustments

• Regular monitoring of renal function, blood glucose levels, and volume status is crucial when using dapagliflozin, especially in patients with renal impairment or those taking insulin or loop diuretics 1.
• Dose adjustments may be necessary to prevent hypoglycemia or excessive diuresis, and patients should be educated on the importance of adhering to their medication regimen and recognizing potential adverse effects 1.
• The use of dapagliflozin in patients with severe renal impairment or those at risk of DKA requires careful consideration and close monitoring by healthcare professionals 1.

From the FDA Drug Label

DAPAGLIFLOZIN TABLETS are not indicated for glycemic control in patients with type 1 diabetes mellitus. Patients with impaired renal function (eGFR less than 60 mL/min/1. 73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. DAPAGLIFLOZIN TABLETS may increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue Use of DAPAGLIFLOZIN TABLETS for glycemic control in patients without established CV disease or CV risk factors is not recommended when eGFR is less than 45 mL/min/1.73 m2 Efficacy and safety trials with dapagliflozin did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis.

Dapagliflozin Contraindications and Warnings:

• Dapagliflozin is not indicated for patients with type 1 diabetes mellitus.
• Loop diuretics may increase the risk of volume depletion or hypotension when used with dapagliflozin.
• Insulin and insulin secretagogues may increase the risk of hypoglycemia when combined with dapagliflozin.
• Impaired renal function (GFR less than 60): patients may be at increased risk for volume depletion or hypotension.
• GFR less than 45: use of dapagliflozin for glycemic control is not recommended in patients without established CV disease or CV risk factors.
• GFR less than 25 or dialysis: efficacy and safety trials did not enroll these patients.
• Ketonuria: dapagliflozin may increase the risk of ketoacidosis, especially in patients with type 1 diabetes mellitus or those with precipitating conditions such as under-insulinization, acute febrile illness, or reduced caloric intake. 2 2

From the Research

Dapagliflozin Contraindications

• Dapagliflozin is not recommended for use in patients with an estimated GFR <60 ml/min/1.73 m(2) 3.
• However, more recent studies have shown that dapagliflozin can be beneficial in patients with chronic kidney disease (CKD), including those with an eGFR of 25-75 ml/min per 1.73 m2 4, 5, 6, 7.
• There is no direct contraindication for the use of dapagliflozin with insulin, but it is essential to monitor renal function before initiation of dapagliflozin 3.
• Loop diuretics can be used with dapagliflozin, but patients should be monitored for signs of dehydration and electrolyte imbalance 4.
• Ketonuria is not a direct contraindication for dapagliflozin, but patients with diabetic ketoacidosis should not be treated with dapagliflozin 3.

Renal Function and Dapagliflozin

• Dapagliflozin may decrease GFR, especially in elderly patients and patients with impaired renal function 3.
• Renal function should be monitored before initiation of dapagliflozin and periodically thereafter 3.
• The effect of dapagliflozin on eGFR slope is more pronounced in patients with higher baseline HbA1c and UACR 7.

Safety and Efficacy of Dapagliflozin

• Dapagliflozin is well tolerated, with the frequency of most adverse events similar to that seen with placebo 3.
• The known safety profile of dapagliflozin was confirmed in the DAPA-CKD trial, with no new safety signals detected 4, 5, 6.
• Dapagliflozin reduces the risk of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic CKD 4, 5.