Side Effects of Metformin
Metformin commonly causes gastrointestinal side effects including diarrhea, nausea, vomiting, abdominal discomfort, and reduced appetite, with lactic acidosis being a rare but serious adverse effect that requires immediate medical attention. 1, 2
Common Gastrointestinal Side Effects
Gastrointestinal disturbances are the most frequently reported side effects of metformin:
- Diarrhea: Affects approximately 30-53% of patients 1, 3
- Nausea/vomiting: Occurs in about 10-26% of patients 1, 3
- Abdominal discomfort/bloating: Reported in 6-8% of patients 1, 3
- Flatulence: Affects approximately 12% of patients 1
- Metallic taste (dysgeusia): Occurs in about 3-7% of patients and typically resolves with continued use 1, 4
- Reduced appetite/anorexia: Reported in approximately 11% of patients 3
These gastrointestinal side effects are often dose-dependent and may be minimized by:
- Starting with a low dose and gradually increasing
- Taking medication with meals
- Using extended-release formulations, which can reduce GI side effects compared to immediate-release formulations 5
Serious Side Effects
Lactic Acidosis
This is a rare but potentially fatal complication with an estimated incidence of less than 1 in 10,000 patients 1. Risk factors include:
- Renal insufficiency (eGFR <30 mL/min/1.73 m²)
- Hepatic impairment
- Heart failure
- Hypoxemic conditions
- Excessive alcohol consumption
- Dehydration
- Advanced age
Warning signs of lactic acidosis include:
- Unusual muscle pain
- Difficulty breathing
- Unusual sleepiness
- Unexplained stomach problems
- Feeling cold (especially in arms and legs)
- Dizziness or lightheadedness
- Slow or irregular heartbeat 1
Vitamin B12 Deficiency
Long-term metformin use can lead to vitamin B12 deficiency, which may contribute to peripheral neuropathy symptoms 2, 1. Regular monitoring of vitamin B12 levels is recommended, particularly in:
- Patients on long-term therapy
- Those with anemia
- Patients with peripheral neuropathy 6
Special Considerations
Renal Function
- Metformin is safe with eGFR ≥30 mL/min/1.73 m²
- Lower doses should be used with eGFR 30-45 mL/min/1.73 m²
- Contraindicated with eGFR <30 mL/min/1.73 m² 2
- Monitor renal function every 3-6 months in at-risk patients 2
Temporary Discontinuation
Metformin should be temporarily discontinued:
- Before procedures using iodinated contrast
- During hospitalizations
- During acute illness that may compromise renal or liver function 2
Hepatic Effects
While rare, metformin-associated hepatotoxicity has been reported 7. Use with caution in patients with impaired hepatic function.
Hypoglycemia
Metformin alone rarely causes hypoglycemia but may occur when combined with:
- Sulfonylureas
- Insulin
- Alcohol consumption 1
Persistence of Side Effects
While most gastrointestinal side effects are transient and occur during the initial phase of treatment, some patients may experience persistent symptoms:
- Approximately 5% of patients may require discontinuation due to intolerable GI side effects 4, 3
- Some patients may develop chronic diarrhea that can be misdiagnosed as irritable bowel syndrome 8
- Side effects can sometimes appear even after prolonged treatment 4
Management of Side Effects
For GI side effects:
- Gradual dose titration
- Taking with meals
- Consider switching to extended-release formulation
- Temporary dose reduction or discontinuation for persistent symptoms
For vitamin B12 deficiency:
- Regular monitoring
- Supplementation if deficient
For suspected lactic acidosis:
- Immediate discontinuation and emergency medical attention
By understanding and anticipating these side effects, appropriate monitoring and management strategies can be implemented to improve medication adherence and patient outcomes.