Does metformin (metformin hydrochloride) cause nephrotoxicity in patients with diabetes mellitus?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Article Review Status
Submitted
Under Review
Approved

Last updated: May 20, 2025 • View editorial policy

From the Guidelines

Metformin generally does not damage kidneys in diabetic patients and is considered safe for most people with diabetes who have normal or mildly impaired kidney function. In fact, metformin may offer kidney protection in diabetic patients by improving glucose control and reducing cardiovascular risk factors, as supported by the most recent guidelines 1. However, metformin should be used with caution in patients with moderate kidney impairment (eGFR 30-45 mL/min) and is contraindicated in severe kidney disease (eGFR below 30 mL/min) because it can accumulate in the body and potentially cause lactic acidosis, a rare but serious side effect.

Some key considerations for the use of metformin in patients with kidney disease include:

  • Metformin is contraindicated in patients with an eGFR < 30 mL/min/1.73 m² 1
  • eGFR should be monitored while taking metformin 1
  • The benefits and risks of continuing treatment should be reassessed when eGFR falls < 45 mL/min/1.73 m² 1
  • Metformin should not be initiated for patients with an eGFR < 45 mL/min/1.73 m² 1
  • Metformin should be temporarily discontinued at the time of or before iodinated contrast imaging procedures in patients with eGFR 30–60 mL/min/1.73 m² 1

For patients with diabetes and kidney disease, healthcare providers typically adjust the metformin dosage based on kidney function, with maximum doses of 1,000-2,000 mg daily for those with mild to moderate impairment. Regular kidney function monitoring is essential for diabetic patients taking metformin, with tests recommended at least annually or more frequently if kidney function is declining, as recommended by recent studies 2, 3, 4. The medication works by reducing glucose production in the liver and improving insulin sensitivity, which helps control blood sugar levels without directly harming the kidneys in most cases.

From the FDA Drug Label

The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 Initiation of metformin hydrochloride tablets is not recommended in patients with eGFR between 30 to 45 mL/min/1. 73 m 2.

Metformin does not directly damage kidneys in diabetic patients. However, renal impairment increases the risk of metformin accumulation and lactic acidosis. The FDA recommends assessing renal function before initiating metformin and monitoring it regularly, especially in patients with eGFR between 30 to 45 mL/min/1.73 m2 5. Severe renal impairment (eGFR below 30 mL/min/1.73 m2) is a contraindication for metformin use 6.

From the Research

Metformin and Kidney Damage in Diabetic Patients

  • The use of metformin in diabetic patients with kidney disease has been a topic of debate due to concerns over lactic acidosis and kidney damage 7, 8, 9.
  • Studies have shown that metformin can be safely used in patients with mild to moderate kidney disease, with estimated glomerular filtration rates (eGFR) between 30-60 mL/min/1.73m2, as long as the dosage is adjusted accordingly 7, 8, 9.
  • However, the use of metformin in patients with severe kidney disease (eGFR < 30 mL/min/1.73m2) is still a controversial issue, with some studies suggesting an increased risk of lactic acidosis and kidney damage 7, 10.
  • A retrospective cohort study found that metformin use was associated with a decreased likelihood of kidney events or death in patients with diabetes and reduced kidney function, compared to sulfonylureas 11.
  • Another study found that continuous metformin treatment in patients with type 2 diabetes and moderate chronic kidney disease may have an adverse effect on renal function 10.

Key Findings

  • Metformin can be safely used in patients with mild to moderate kidney disease, with adjusted dosages 7, 8, 9.
  • The use of metformin in patients with severe kidney disease is still a controversial issue 7, 10.
  • Metformin may have a protective effect on kidney function in patients with diabetes and reduced kidney function, compared to sulfonylureas 11.
  • Continuous metformin treatment may have an adverse effect on renal function in patients with type 2 diabetes and moderate chronic kidney disease 10.

Study Limitations

  • The studies had varying sample sizes and follow-up periods, which may affect the generalizability of the results 7, 8, 9, 11, 10.
  • The studies used different methodologies and outcome measures, which may make it difficult to compare the results directly 7, 8, 9, 11, 10.

Related Questions

Can metformin (metformin hydrochloride) be discontinued after resolution of impaired glucose regulation (prediabetes)?
What medications are suitable for people with Impaired renal function (Chronic Kidney Disease, CKD) and Diabetes Mellitus Type 2?
What medication should a 75-year-old woman with Impaired renal function, type 2 diabetes (Diabetes Mellitus type 2), hypertension, hyperlipidemia, and stage 3 Chronic Kidney Disease (CKD) stop taking after being discharged from the hospital with a diagnosis of community-acquired pneumonia, and prescribed atorvastatin, cefuroxime, amlodipine, extended-release metformin (Metformin Hydrochloride), and extended-release metoprolol succinate (Metoprolol Succinate)?
What is the management plan for an 84-year-old female with type 2 diabetes mellitus, HbA1c of 6.7%, and mild impaired renal function on metformin 500mg bid?
Does metformin (Metformin Hydrochloride) affect kidney function in terms of estimated Glomerular Filtration Rate (eGFR)?
Does glicazide (a sulfonylurea) cause nephrotoxicity in patients with diabetes mellitus?
Is Prometrium (progesterone) used in the treatment of Polycystic Ovary Syndrome (PCOS)?
Is betamethasone (betamethasone) ointment too potent for a suspected secondary syphilis (Sexually Transmitted Infection) rash on the dorsal hands in a patient with no other symptoms who has recently completed Benzathine penicillin G (BCN, Bicillin) treatment?
What is the use of Medroxyprogesterone (MPA), a synthetic Progestin?
What is the role of Medroxyprogesterone (Progestin) in Hormone Replacement Therapy (HRT) for menopause?
What is the treatment approach for a patient with Alzheimer's disease (AD) presenting to the emergency room with aggressive behavioral changes?

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.