Common Side Effects of Metformin
The most common side effects of metformin include gastrointestinal disturbances such as diarrhea, nausea, vomiting, abdominal discomfort, and flatulence, which typically occur in up to 53% of patients but generally improve with continued use. 1
Gastrointestinal Side Effects
- Diarrhea is the most prevalent side effect, occurring in approximately 53% of patients compared to 12% with placebo 1
- Nausea and vomiting affect about 26% of patients versus 8% with placebo 1
- Flatulence occurs in approximately 12% of patients compared to 6% with placebo 1
- Abdominal discomfort affects about 6% of patients versus 5% with placebo 1
- Indigestion is reported in approximately 7% of patients versus 4% with placebo 1
- These GI side effects typically improve after taking the medication for a while 1
- Taking metformin with meals can help reduce these gastrointestinal effects 1
Other Common Side Effects
- Metallic taste in the mouth occurs in approximately 3% of patients when starting metformin therapy 1
- Asthenia (weakness) affects about 9% of patients versus 6% with placebo 1
- Headache occurs in approximately 6% of patients versus 5% with placebo 1
- Vitamin B12 deficiency can develop with long-term use, requiring periodic monitoring 2, 3
Management Strategies for GI Side Effects
- Start with a low dose and gradually increase (slow titration) to minimize gastrointestinal side effects 2
- Consider extended-release formulations, which may reduce GI side effects compared to immediate-release formulations 4, 5
- Taking medication with meals can help reduce gastrointestinal symptoms 1
- Probiotics may help reduce the risk of diarrhea, bloating, and constipation when added to metformin therapy 6
- Temporary discontinuation may be necessary during acute illness 2
Serious but Rare Side Effects
- Lactic acidosis is a rare but potentially fatal complication (less than 1 case per 100,000 treated patients) 3, 2
- Risk factors for lactic acidosis include severe kidney problems (eGFR <30 mL/min/1.73 m²), liver impairment, heart failure, and excessive alcohol consumption 2, 1
- Symptoms of lactic acidosis include unexplained hyperventilation, myalgias, malaise, unusual somnolence, cold extremities, dizziness, and irregular heartbeat 1
Special Considerations
- Metformin rarely causes hypoglycemia when used as monotherapy but can cause hypoglycemia when combined with sulfonylureas or insulin 1
- Metformin should be temporarily discontinued before surgical procedures or radiological procedures involving iodinated contrast agents 1
- Alcohol should be limited while taking metformin as it increases the risk of lactic acidosis 1
- Metformin may be safely used in patients with eGFR as low as 30 mL/min/1.73 m² 3
Clinical Pearls
- Diarrhea caused by metformin can be chronic and may be misdiagnosed as irritable bowel syndrome 7
- Approximately 6% of patients discontinue metformin due to diarrhea 1
- Metformin-induced GI side effects are mainly due to alterations in gut microbiota, raised intestinal glucose, and increased ileal bile salt reabsorption 7
- Extended-release formulations have shown fewer GI side effects compared to immediate-release formulations at comparable doses 4
By understanding these common side effects and implementing appropriate management strategies, healthcare providers can help improve medication adherence and optimize diabetes management for patients on metformin therapy.