Should dapagliflozin (Forxiga) be withheld in acute illness?

From the Guidelines

Yes, dapagliflozin should be temporarily withheld during acute illness, especially when the illness involves dehydration, reduced oral intake, or risk of volume depletion. This recommendation is based on the most recent and highest quality study, which suggests that SGLT2 inhibitors like dapagliflozin can exacerbate volume depletion during illness and increase the risk of euglycemic diabetic ketoacidosis 1.

Rationale for Withholding Dapagliflozin

The rationale for withholding dapagliflozin during acute illness is to prevent potential complications such as:

• Dehydration
• Hypotension
• Acute kidney injury These medications work by increasing glucose excretion through the kidneys, which can exacerbate volume depletion during illness. Additionally, there is concern about the increased risk of euglycemic diabetic ketoacidosis during periods of physiological stress, particularly when insulin doses are reduced or carbohydrate intake is limited.

Guidance for Patients

Patients should be advised to stop taking dapagliflozin at the first sign of acute illness and contact their healthcare provider for guidance on when to resume the medication. Typically, dapagliflozin can be restarted once the patient has fully recovered from the acute illness and has resumed normal eating and drinking patterns.

Supporting Evidence

The KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease recommends temporarily withholding SGLT2 inhibitors during acute illness, especially when the illness involves dehydration, reduced oral intake, or risk of volume depletion 1. Other studies have also highlighted the importance of cautious use of SGLT2 inhibitors in patients with acute illness, particularly those with reduced renal function or at risk of volume depletion 1.

Key Considerations

When deciding whether to withhold dapagliflozin during acute illness, healthcare providers should consider the following key factors:

• The severity of the illness and the risk of volume depletion
• The patient's renal function and the potential for acute kidney injury
• The risk of euglycemic diabetic ketoacidosis, particularly in patients with reduced insulin doses or limited carbohydrate intake By taking a cautious approach and temporarily withholding dapagliflozin during acute illness, healthcare providers can help minimize the risk of potential complications and ensure the best possible outcomes for their patients.

From the FDA Drug Label

Withhold DAPAGLIFLOZIN TABLETS, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include ... acute febrile illness...

Withholding dapagliflozin in acute illness is recommended if the situation could predispose the patient to ketoacidosis, such as acute febrile illness. 2

From the Research

Dapagliflozin Use in Acute Illness

• The decision to withhold dapagliflozin in acute illness is complex and depends on various factors, including the patient's renal function and the severity of the illness 3, 4.
• Studies have shown that dapagliflozin is generally well-tolerated and does not increase the risk of acute renal toxicity or deterioration of renal function in patients with normal or mildly impaired renal function 3.
• However, in patients with moderate or severe renal impairment, dapagliflozin is not recommended due to the increased risk of renal adverse events 4, 5.
• In the context of acute illness, such as renal ischemia/reperfusion injury, dapagliflozin has been shown to have protective effects on renal function by alleviating oxidative stress and inflammation 6.
• Additionally, a study found that dapagliflozin use was associated with a lower risk of post-contrast acute kidney injury in patients with type 2 diabetes and chronic kidney disease undergoing an elective coronary procedure 7.

Renal Function and Dapagliflozin

• Dapagliflozin's effects on renal function are mediated by inhibition of renal sodium-glucose cotransporter-2, which increases urinary glucose excretion and reduces blood glucose levels 3, 4.
• Studies have shown that dapagliflozin does not adversely affect renal function in patients with normal or mildly impaired renal function, but may increase the risk of renal adverse events in patients with moderate or severe renal impairment 3, 4.
• The use of dapagliflozin in patients with acute illness requires careful consideration of the patient's renal function and the potential risks and benefits of continued treatment 3, 4, 7.

Clinical Considerations

• When deciding whether to withhold dapagliflozin in acute illness, clinicians should consider the patient's individual characteristics, including renal function, severity of illness, and concomitant medications 3, 4, 7.
• Close monitoring of renal function and adjustment of dapagliflozin dosage or discontinuation of treatment may be necessary in patients with acute illness or renal impairment 3, 4, 7.