From the Guidelines
Metformin is associated with gastrointestinal side effects, including bloating, abdominal discomfort, and diarrhea, which can be mitigated by gradual dose titration and/or using extended-release formulation, as reported in the most recent study 1. The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration and/or using extended-release formulation.
- The drug is cleared by kidney filtration, and metformin may be safely used in people with estimated glomerular filtration rate ≥30 mL/min/1.73 m² 1.
- Very high circulating levels (e.g., as a result of overdose or acute kidney injury) have been associated with lactic acidosis 1.
- However, the occurrence of this complication is very rare and primarily occurs when the estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m² 1.
- Metformin use is also associated with increased risk of vitamin B12 deficiency and worsening of symptoms of neuropathy, suggesting periodic testing of vitamin B12 levels 1. The medication should be used with caution in patients with kidney disease, and the dose should be adjusted accordingly to minimize the risk of lactic acidosis.
- Most side effects are mild and transient, with many patients experiencing improved tolerance after several weeks of consistent use. The benefits of metformin, including its efficacy in reducing microvascular complications, cardiovascular events, and death, outweigh the risks of side effects, making it a commonly used medication for the treatment of type 2 diabetes 1.
From the FDA Drug Label
Metformin hydrochloride, the medicine in metformin hydrochloride tablets, can cause a rare, but serious, side effect called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. Common side effects of metformin hydrochloride tablets include diarrhea, nausea, and upset stomach. About 3 out of every 100 people who take metformin hydrochloride tablets have an unpleasant metallic taste when they start taking the medicine. Metformin hydrochloride tablets rarely cause hypoglycemia (low blood sugar) by themselves. However, hypoglycemia can happen if you do not eat enough, if you drink alcohol, or if you take other medicines to lower blood sugar.
The common side effects of metformin include:
- Diarrhea
- Nausea
- Upset stomach
- Unpleasant metallic taste
- Hypoglycemia (low blood sugar)
The serious side effect of metformin is:
- Lactic acidosis (a build-up of lactic acid in the blood) that can cause death.
It is essential to monitor for symptoms of lactic acidosis, such as:
- Feeling very weak and tired
- Unusual muscle pain
- Trouble breathing
- Unusual sleepiness or sleep longer than usual
- Unexplained stomach or intestinal problems with nausea and vomiting, or diarrhea
- Feeling cold, especially in your arms and legs
- Feeling dizzy or lightheaded
- Having a slow or irregular heartbeat
From the Research
Metformin Side Effects
- The most common side effects of metformin are not explicitly stated in the provided studies, but it is mentioned that metformin is generally well-tolerated with minimal side effects 3.
- Lactic acidosis has been associated with the use of metformin, but the incidence is very rare, with a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users 4.
- Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects 4.
- Hypoglycemia is not a major concern with metformin, as the adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23-3.50) compared with current metformin use, indicating a lower risk of hypoglycemia with metformin 4.
- Other benefits of metformin include improvements in certain lipids, inflammatory markers, and a reduction in cardiovascular events, apparently independent from the drug's glucose-lowering effect 5.
Comparison with Other Medications
- Metformin has been compared to other antidiabetic medications, such as sulfonylureas, and has been shown to have a lower risk of hypoglycemia 4.
- The fixed-dose combination of metformin and pioglitazone appears to be a good option for treating diabetes in insulin-resistant patients, with advantages in terms of glycemic control and other cardiovascular risk factors frequently associated with diabetes 6.
Clinical Use
- Metformin is widely considered to be the optimal initial therapy for patients with type 2 diabetes mellitus, due to its efficacy, low cost, weight neutrality, and good safety profile 5.
- However, the emergence of newer antidiabetic medications with more robust evidence for cardioprotection has prompted re-evaluation of metformin as the initial therapy for all patients with diabetes 7, 3.