Side Effects of Metformin
Metformin commonly causes gastrointestinal side effects and rarely can lead to serious complications such as lactic acidosis, particularly in patients with renal insufficiency, requiring careful monitoring and appropriate patient selection. 1
Common Side Effects
Gastrointestinal Side Effects
- Diarrhea (53% of patients) 2
- Nausea/vomiting (26% of patients) 2
- Flatulence (12% of patients) 2
- Indigestion (7% of patients) 2
- Abdominal discomfort (6% of patients) 2
These gastrointestinal side effects are typically mild and transient, often resolving with continued use. They can be minimized by:
- Starting with a low dose and gradually titrating upward
- Taking metformin with meals
- Using extended-release formulations, which may improve GI tolerability 3
Other Common Side Effects
- Metallic taste (occurs in approximately 3% of patients) 2
- Asthenia/weakness (9% of patients) 2
- Headache (6% of patients) 2
Serious Side Effects
Lactic Acidosis
Lactic acidosis is a rare but potentially fatal complication with symptoms including:
- Cold hands or feet
- Dizziness or lightheadedness
- Slow or irregular heartbeat
- Extreme weakness or fatigue
- Breathing difficulties
- Drowsiness
- Stomach pain, nausea, or vomiting 2
Risk factors for lactic acidosis include:
- Severe kidney problems (eGFR <30 mL/min/1.73 m²)
- Liver problems
- Excessive alcohol consumption
- Dehydration
- Recent surgery
- Heart attack, severe infection, or stroke 2
Vitamin B12 Deficiency
- Long-term metformin use can lead to vitamin B12 deficiency 1, 2
- Regular monitoring of vitamin B12 levels is recommended for patients on long-term therapy 1
Hypoglycemia Risk
- Metformin rarely causes hypoglycemia when used as monotherapy 2, 4
- However, hypoglycemia can occur when:
- Combined with other glucose-lowering medications
- Inadequate caloric intake
- Excessive alcohol consumption 2
Special Considerations
Renal Function
- Metformin is contraindicated in patients with eGFR <30 mL/min/1.73 m² 1
- Patients with eGFR 30-45 mL/min/1.73 m² should use lower doses with careful monitoring 1
- Regular monitoring of renal function is recommended every 3-6 months in at-risk patients 1
Alcohol Consumption
- Excessive alcohol intake significantly increases the risk of lactic acidosis 1, 2
- Patients should be advised against binge drinking or regular heavy alcohol consumption 1
Temporary Discontinuation
Metformin should be temporarily discontinued during:
- Procedures using iodinated contrast
- Hospitalizations
- Acute illness that may compromise renal or liver function 1
Management of Side Effects
- For persistent GI side effects, dose reduction or discontinuation should be considered 1
- Switching from immediate-release to extended-release formulations may reduce GI side effects 3
- In some cases, chronic diarrhea from metformin may be misdiagnosed as irritable bowel syndrome 5
By understanding these potential side effects and implementing appropriate monitoring and management strategies, the risks associated with metformin therapy can be minimized while maintaining its therapeutic benefits.