From the Guidelines
Metformin commonly causes 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 minimized by:
- Gradual dose titration
- Using extended-release formulation Some key points to consider when prescribing metformin include:
- Starting with a low dose (typically 500 mg once daily with dinner) and gradually increasing to the target dose (usually 1000-2000 mg daily in divided doses) over several weeks
- Taking metformin with meals rather than on an empty stomach to reduce gastrointestinal distress
- Using extended-release formulations (Metformin ER/XR) which often cause fewer side effects than immediate-release versions and can be taken once daily, improving tolerance and adherence
- Monitoring for vitamin B12 deficiency, which can occur with long-term use, and supplementing if needed, as suggested by 1 and 1
- Being aware of the rare but serious side effect of lactic acidosis, which primarily occurs in patients with contraindications such as kidney disease, liver disease, or heart failure, and taking steps to prevent this, such as temporarily discontinuing metformin during acute illness, before procedures requiring contrast dye, or during periods of dehydration. Most gastrointestinal side effects are transient and resolve within the first few weeks of treatment as the body adjusts to the medication, so patients should be encouraged to persist through the initial adjustment period if possible, as indicated by the latest evidence 1.
From the FDA Drug Label
Common side effects of metformin hydrochloride tablets include diarrhea, nausea, and upset stomach. These side effects generally go away after you take the medicine for a while. Taking your medicine with meals can help reduce these side effects.
About 3 out of every 100 people who take metformin hydrochloride tablets have an unpleasant metallic taste when they start taking the medicine. It lasts for a short time.
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.
Lactic acidosis, a rare but serious condition, can occur due to metformin use. Symptoms include feeling cold, dizzy, weak, or tired, having trouble breathing, or experiencing stomach pains, nausea, or vomiting.
Common side effects of metformin include:
- Diarrhea
- Nausea
- Upset stomach
- Unpleasant metallic taste (in about 3% of patients)
- Hypoglycemia (low blood sugar, although rare when metformin is used alone)
To minimize side effects:
- Take metformin with meals to reduce gastrointestinal side effects
- Avoid drinking excessive alcohol, as it can increase the risk of lactic acidosis
- Monitor blood sugar levels and report any symptoms of hypoglycemia to your doctor
- Stay hydrated and avoid dehydration, which can increase the risk of lactic acidosis 2 2
From the Research
Common Side Effects of Metformin
- The most common adverse effects associated with metformin are mild, transient gastrointestinal symptoms, which are usually self-limiting 3.
- These side effects include diarrhea, nausea, vomiting, abdominal pain, flatulence, and bloating 4, 5, 6.
- Metformin-induced chronic diarrhea can be misdiagnosed as irritable bowel syndrome, highlighting the importance of considering this potential side effect in patients with type 2 diabetes taking metformin 7.
Minimizing Side Effects
- Side effects can be minimized by initiating metformin therapy at a low dose and gradually titrating upward, and by taking metformin with meals 3.
- Adding probiotics to metformin therapy can decrease the risk of diarrhea, bloating, and constipation 4.
- Switching from immediate-release metformin to extended-release metformin can also reduce the frequency of gastrointestinal side effects 5.
- Temporary discontinuation, dose titration, or proper intake of medicine can be tried before extensive evaluation of any GI problem in patients on metformin 6.
Prevalence of Side Effects
- Approximately 20% of metformin users experience gastrointestinal adverse events 4.
- A study found that 51.66% of patients presented with GI side effects, including diarrhea, nausea/vomiting, pain abdomen, flatulence, retching, and dysgeusia 6.
- Gastrointestinal side effects can occur even after prolonged treatment with metformin 6.