Management of Metformin During Acute Illness

Critical Action: Immediate Discontinuation

• The American Journal of Kidney Diseases and Kidney International recommend that metformin must be temporarily discontinued immediately when patients with type 2 diabetes develop any acute illness that increases the risk of acute kidney injury (AKI), including serious infections, dehydration, vomiting, diarrhea, or conditions causing hypoperfusion or hypoxemia 1, 2
• The Canadian Society of Nephrology explicitly recommends temporary discontinuation of metformin in patients with eGFR <60 mL/min/1.73 m² who have serious intercurrent illness that increases AKI risk, but this principle applies to all patients on metformin during acute illness, regardless of baseline renal function 1, 5

Rationale: Risk of Metformin-Associated Lactic Acidosis (MALA)

• The FDA label explicitly warns that metformin should be discontinued when acute illness occurs because most episodes of metformin-associated lactic acidosis develop concurrent with other acute illness, often when AKI contributes to reduced metformin clearance 2, 3, 4

Additional Considerations for Patients with Baseline Renal Impairment

• For patients with chronic kidney disease (CKD) who develop acute illness, metformin dose reduction should be considered at baseline if comorbidities place them at increased risk of lactic acidosis due to hypoperfusion/hypoxemia; discontinue during any acute illness 2, 3, 4
• For patients with eGFR 45-59 mL/min/1.73 m², metformin dose reduction should be considered at baseline; discontinue during any acute illness 2, 3, 4
• For patients with eGFR 30-44 mL/min/1.73 m², baseline dose should already be reduced to 1000 mg daily; discontinue immediately during acute illness 2, 3, 4
• For patients with eGFR <30 mL/min/1.73 m², metformin is contraindicated and should not be used 2, 3, 4

Concomitant Medications That Increase Risk

• The American Journal of Kidney Diseases recommends discontinuing or holding ACE inhibitors, ARBs, diuretics, NSAIDs, aldosterone inhibitors, and direct renin inhibitors along with metformin during acute illness in patients with eGFR <60 mL/min/1.73 m² 1

When to Restart Metformin After Acute Illness

• Metformin should not be restarted until complete resolution of the acute illness, lactic acidosis has resolved, renal function has returned to baseline or stabilized, eGFR ≥30 mL/min/1.73 m², and the patient is hemodynamically stable 2, 3, 4