When to restart metformin (Metformin) and Farxiga (Dapagliflozin) post-operatively?

From the Guidelines

Metformin and Farxiga (dapagliflozin) should typically be restarted 48 hours after surgery, once the patient is eating normally and kidney function has been assessed as normal, with metformin requiring an eGFR >30 mL/min/1.73m² and Farxiga requiring an eGFR >45 mL/min/1.73m², as recommended by recent guidelines 1. When considering the restart of these medications, it is crucial to ensure the patient is hemodynamically stable, well-hydrated, and not showing signs of acute kidney injury or infection. The risk of lactic acidosis with metformin, although found not to be significantly associated with its use in recent data 1, and the risk of volume depletion and urinary tract infections with Farxiga, must be carefully weighed against the benefits of restarting these medications.

Key Considerations for Restarting Metformin and Farxiga

• Ensure the patient is clinically stable and has resumed a normal diet before restarting SGLT2 inhibitors like Farxiga, as suggested by the 2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM guideline 1.
• For metformin, recent data indicates it is not associated with lactic acidosis, but caution is still advised in patients with risk factors such as renal failure or severe heart failure 1.
• Monitor blood glucose levels closely during the perioperative period and use alternative glycemic control methods until metformin and Farxiga can be safely restarted, aiming for a blood glucose target range of 80–180 mg/dL (4.4–10.0 mmol/L) as suggested by the standards of medical care in diabetes-2021 1.

Adjusting the Timing Based on Surgical Procedure

The timing of restarting metformin and Farxiga may need adjustment based on the specific surgical procedure, with longer delays recommended after major surgeries or those involving contrast dye. It is essential to consider the individual patient's risk factors and the nature of the surgery when deciding on the optimal time to restart these medications.

Resuming Medications

Resume metformin and Farxiga at the pre-operative dose unless the clinical situation suggests a need for adjustment. Continuous monitoring for signs of hyperglycemia, volume depletion, and other potential complications is crucial during the perioperative period. The decision to restart these medications should always prioritize minimizing morbidity, mortality, and improving the quality of life for the patient.

From the FDA Drug Label

1. 4 Temporary Interruption for Surgery Withhold DAPAGLIFLOZIN TABLETS for at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. Resume DAPAGLIFLOZIN TABLETS when the patient is clinically stable and has resumed oral intake [see Warnings and Precautions (5.1) and Clinical Pharmacology (12. 2)].

Surgery and other procedures —Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment. Metformin hydrochloride tablets should be temporarily discontinued while patients have restricted food and fluid intake

Restarting Metformin and Farxiga post-operatively:

• Farxiga (Dapagliflozin): Resume when the patient is clinically stable and has resumed oral intake 2.
• Metformin: Restart when the patient no longer has restricted food and fluid intake, ensuring that renal function is stable 3.

From the Research

Restarting Metformin Post-Operatively

• The optimal time to restart metformin has not been well-studied 4.
• It is reasonable to first ensure that lactic acidosis has resolved, and then recheck the kidney function post-recovery from critical illness, ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m2 or better before restarting metformin 4.
• For patients who have been on a biguanide (such as metformin) before admission, these agents often are restarted in the postoperative period when oral intake of medications is possible and hepatic and renal function are stable 5.

Restarting Farxiga (Dapagliflozin) Post-Operatively

• There is no direct evidence provided for restarting Farxiga (Dapagliflozin) post-operatively.
• However, the general principles of restarting oral glucose-lowering agents, such as ensuring oral intake of medications is possible and hepatic and renal function are stable, may apply 5.

Considerations for Metformin Use

• Metformin may have an adverse effect on renal function in patients with type 2 diabetes mellitus and moderate chronic kidney disease 6.
• Metformin-associated lactic acidosis (MALA) can occur in the absence of renal impairment, systemic hypoperfusion, or severe liver disease 7.
• The development of MALA, although rare, should be kept in mind to prevent potentially life-threatening toxicity 7.