Introduction to Metformin Side Effects
As one of the most prescribed medications for type 2 diabetes, metformin (Glucophage) is generally well-tolerated but can cause various side effects ranging from mild gastrointestinal discomfort to rare but serious complications. This guide provides a detailed, evidence-based analysis of all potential adverse effects, their mechanisms, risk factors, and clinical management strategies.
1. Common Side Effects (≥10% of patients)
Gastrointestinal Disturbances
Approximately 30% of patients experience GI symptoms, typically during treatment initiation or dose escalation:
Most Frequent GI Effects:
- Diarrhea (25-30% of patients) - Caused by altered intestinal glucose metabolism and gut microbiota changes
- Nausea/Vomiting (10-20%) - Often related to rapid dose titration
- Abdominal discomfort (10-15%) - Includes cramping and bloating
- Metallic taste (3-5%) - Less common but distinctive effect
Management Strategies for GI Effects:
- Initiate therapy with 500mg once daily with evening meal
- Gradually increase dose over 4-6 weeks
- Switch to extended-release formulation if persistent
- Ensure adequate hydration during diarrhea episodes
2. Serious Adverse Effects
Lactic Acidosis
Although rare (incidence 3-10 cases per 100,000 patient-years), lactic acidosis represents the most concerning potential complication:
Primary Risk Factors:
- Renal impairment (eGFR <30 mL/min)
- Acute illness with dehydration
- Excessive alcohol consumption
- Concurrent use of nephrotoxic drugs
Clinical Presentation:
- Unexplained hyperventilation or respiratory distress
- Severe fatigue and muscle pain
- Hypothermia
- Hypotension with bradycardia
3. Long-Term Considerations
Vitamin B12 Deficiency
Chronic metformin use (≥4 years) is associated with B12 deficiency in 10-30% of patients due to:
- Interference with calcium-dependent B12 absorption
- Altered gut microbiota affecting intrinsic factor
Monitoring Recommendations:
- Annual B12 levels for patients on long-term therapy
- Consider prophylactic supplementation in high-risk groups
- Monitor for megaloblastic anemia and neuropathy
Clinical Takeaways
- Most side effects are mild and transient
- Proper dose titration minimizes GI intolerance
- Regular monitoring prevents serious complications
- Extended-release formulations improve tolerability