Should I hold metformin (a biguanide oral hypoglycemic agent) in a patient with weakness and acute kidney injury (AKI)?

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From the Guidelines

Yes, you should hold metformin in a patient with weakness and acute kidney injury (AKI). Metformin should be temporarily discontinued until the AKI resolves and kidney function returns to baseline. This is because metformin is primarily eliminated by the kidneys, and reduced kidney function leads to drug accumulation, increasing the risk of lactic acidosis—a rare but serious side effect with high mortality 1. The patient's weakness could potentially be a symptom of early lactic acidosis or could worsen due to metformin's continued use during compromised kidney function.

Key Considerations

  • Monitor the patient's kidney function with serum creatinine and estimated glomerular filtration rate (eGFR) 1.
  • Metformin can typically be restarted once kidney function stabilizes and eGFR is consistently above 30 mL/min/1.73m² 1.
  • During this temporary discontinuation, the patient's blood glucose should be managed with alternative agents such as insulin.
  • When restarting metformin after AKI resolution, consider beginning at a lower dose and titrating up as tolerated while continuing to monitor kidney function 1.

Rationale

The risk of lactic acidosis associated with metformin use in patients with renal impairment is a significant concern, with a mortality rate ranging from 30–50% 1. Given the potential for severe consequences, it is prudent to err on the side of caution and discontinue metformin in patients with AKI until kidney function recovers. This approach prioritizes the patient's safety and minimizes the risk of lactic acidosis, aligning with the principles of minimizing morbidity, mortality, and optimizing quality of life.

From the FDA Drug Label

Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1. 73 m 2, assess the benefit and risk of continuing therapy. Discontinue metformin hydrochloride tablets if the patient's eGFR later falls below 30 mL/minute/1.73 m 2

The patient has acute kidney injury (AKI), which may indicate a decreased eGFR. Given the potential risk of lactic acidosis associated with metformin use in patients with renal impairment, it is recommended to hold metformin in this patient until renal function is stabilized and the benefit-risk of continuing therapy can be reassessed 2.

From the Research

Metformin and Acute Kidney Injury (AKI)

  • Metformin is a biguanide oral hypoglycemic agent that can cause lactic acidosis, especially in patients with acute kidney injury (AKI) or chronic kidney disease (CKD) 3, 4.
  • The development of metformin-induced AKI should be considered in patients with several AKI risk factors who are taking metformin, including dehydration, alcohol consumption, and the use of certain medications such as angiotensin receptor blockers or SGLT2 inhibitors 3.
  • Metformin-related lactic acidosis (MALA) is a rare but potentially fatal adverse effect of metformin, particularly in patients with AKI, and should always be considered in clinical practice 4.

Management of Metformin-Associated Lactic Acidosis

  • Dialysis, including intermittent hemodialysis and continuous renal replacement therapy, can contribute significantly to the management of metformin-associated lactic acidosis and improvement in outcome 4, 5, 6.
  • Prolonged intermittent hemodialysis may be effective in treating metformin intoxication complicated by lactic acidosis and AKI 5.
  • Accurate recognition of metformin-associated lactic acidosis and prompt initiation of dialysis are paramount steps towards rapid recovery 6.

Considerations for Holding Metformin in Patients with Weakness and AKI

  • Given the potential for metformin to cause or exacerbate lactic acidosis in patients with AKI, it may be necessary to hold metformin in patients with weakness and AKI, especially if they have other risk factors for metformin-induced AKI 3, 4.
  • A thorough evaluation of the patient's renal function and other potential causes of AKI should be performed before making a decision to hold metformin 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Metformin-related lactic acidosis in patients with acute kidney injury.

International urology and nephrology, 2011

Research

Treatment of Metformin Intoxication Complicated by Lactic Acidosis and Acute Kidney Injury: The Role of Prolonged Intermittent Hemodialysis.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2017

Research

Acute Kidney Injury.

Primary care, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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