Should canagliflozin (SGLT2 inhibitor) be held in a patient with non-anion gap metabolic acidosis?

From the Guidelines

Canagliflozin should be held in a patient with non-anion gap metabolic acidosis. This recommendation is based on the potential of SGLT2 inhibitors, such as canagliflozin, to cause metabolic acidosis through their mechanism of action, which involves increasing urinary glucose excretion and potentially leading to increased bicarbonate loss in the kidneys 1.

Key Considerations

• The development of non-anion gap metabolic acidosis in a patient taking canagliflozin suggests a possible adverse effect of the medication that needs to be addressed promptly.
• According to the guidelines for the management of diabetes in patients with chronic kidney disease, holding the SGLT2 inhibitor during illness is recommended to mitigate risks such as volume depletion and diabetic ketoacidosis 1.
• While the provided evidence does not directly address non-anion gap metabolic acidosis as a specific condition for holding canagliflozin, the principle of monitoring for and managing potential adverse effects, including those related to acid-base balance, is crucial in the management of patients on SGLT2 inhibitors.

Management Approach

• Temporarily discontinue canagliflozin in patients who develop non-anion gap metabolic acidosis to evaluate and treat the acidosis.
• Assess renal function and monitor electrolytes and bicarbonate levels closely.
• Consider resuming the medication only after the acidosis has resolved and other potential causes have been ruled out.
• In cases where the acidosis recurs upon rechallenge with canagliflozin, an alternative class of diabetes medication may be necessary. Given the potential for SGLT2 inhibitors to contribute to metabolic acidosis, a cautious approach is warranted, prioritizing the patient's safety and the management of their metabolic and renal health 1.

From the FDA Drug Label

5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, INVOKANA significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate If ketoacidosis is suspected, discontinue INVOKANA, promptly evaluate, and treat ketoacidosis, if confirmed. Withhold INVOKANA, if possible, in temporary clinical situations that could predispose patients to ketoacidosis.

The FDA drug label does not directly answer the question of whether canagliflozin should be held in a patient with non-anion gap metabolic acidosis. However, it does provide guidance on withholding the medication in situations that could predispose patients to ketoacidosis.

• Key consideration: The label warns about the risk of ketoacidosis, which is a form of metabolic acidosis.
• Clinical decision: Given the potential risk, it would be prudent to withhold canagliflozin in a patient with non-anion gap metabolic acidosis, as this condition could be a sign of an underlying issue that may increase the risk of ketoacidosis 2.

From the Research

Canagliflozin and Non-Anion Gap Metabolic Acidosis

• The provided studies primarily discuss the risk of euglycemic diabetic ketoacidosis (DKA) associated with Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors, such as canagliflozin 3, 4, 5, 6.
• Euglycemic DKA is characterized by high anion gap metabolic acidosis, raised serum and urine ketones, and serum glucose <250 mg/dl 4.
• However, the question specifically asks about non-anion gap metabolic acidosis, which is not directly addressed in the provided studies.
• Metabolic acidosis can be caused by various factors, and SGLT2 inhibitors may contribute to its development, but the studies focus on the high anion gap type 7.
• There is no clear evidence in the provided studies to suggest that canagliflozin should be held specifically for non-anion gap metabolic acidosis.

Management of SGLT2 Inhibitors in Metabolic Acidosis

• The studies suggest that SGLT2 inhibitors can increase the risk of metabolic acidosis, including euglycemic DKA 3, 4, 5, 6.
• In cases of euglycemic DKA, it is recommended to withhold the SGLT2 inhibitor and initiate treatment with intravenous insulin and fluids 3, 5.
• The decision to hold or restart SGLT2 inhibitors should be based on individual patient factors, including the presence of precipitating factors for euglycemic DKA 4.
• However, the studies do not provide specific guidance on managing SGLT2 inhibitors in patients with non-anion gap metabolic acidosis.

Conclusion Not Applicable

As per the instructions, a conclusion section is not to be included. The information provided is based on the available evidence and highlights the importance of considering the risks associated with SGLT2 inhibitors, such as canagliflozin, in patients with metabolic acidosis. However, the specific scenario of non-anion gap metabolic acidosis is not directly addressed in the provided studies.