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. These symptoms are the principal side effects of metformin, as reported in the most recent study 1. The study, published in 2025, highlights that metformin is effective and safe, reducing risks of microvascular complications, cardiovascular events, and death.
The gastrointestinal side effects of metformin can be managed by taking the medication with meals and starting with a low dose that gradually increases over several weeks. Less common side effects include vitamin B12 deficiency with long-term use, which may require supplementation, as suggested by 1 and 1. Lactic acidosis is a rare but serious side effect that primarily affects patients with kidney disease, liver disease, or heart failure.
Key points to consider when prescribing metformin include:
- Starting with a low dose, such as 500mg once daily, and gradually increasing as tolerated
- Using extended-release formulations to minimize gastrointestinal side effects
- Monitoring vitamin B12 levels, particularly in patients with anemia or neuropathy
- Avoiding metformin in patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²
- Advising patients to avoid excessive alcohol consumption while taking metformin to reduce the risk of lactic acidosis.
Overall, metformin is a commonly used and effective medication for the management of type 2 diabetes, with a favorable safety profile when used appropriately, as supported by the most recent 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. Adverse reactions reported in greater than 5% of metformin hydrochloride tablets treated patients and that were more common than in placebo-treated patients, are listed in Table 1 Table 1: Adverse Reactions from a Clinical Trial of Metformin Hydrochloride TabletsOccurring >5% and More Common than Placebo in Patients with Type 2 Diabetes Mellitus Metformin Hydrochloride Tablets (n=141) Placebo (n=145) Diarrhea 53% 12% Nausea/Vomiting 26% 8% Flatulence 12% 6% Asthenia 9% 6% Indigestion 7% 4% Abdominal Discomfort 6% 5% Headache 6% 5%
The common side effects of Metformin include:
- Diarrhea
- Nausea
- Upset stomach
- Flatulence
- Asthenia
- Indigestion
- Abdominal Discomfort
- Headache These side effects generally go away after taking the medicine for a while. Taking the medicine with meals can help reduce these side effects 2.
From the Research
Common Side Effects of Metformin
The common side effects of metformin, a biguanide used to treat type 2 diabetes, include:
- Gastrointestinal side effects such as diarrhea, nausea, vomiting, abdominal bloating, flatulence, and heartburn 3, 4, 5, 6
- Lactic acidosis, a rare but serious side effect, which is more likely to occur in patients with chronic renal failure 4, 7
Gastrointestinal Side Effects
Gastrointestinal side effects are the most common side effects of metformin, affecting up to 51.66% of patients 5. These side effects can include:
- Diarrhea (33 patients out of 120) 5
- Nausea/vomiting (28 patients out of 120) 5
- Pain abdomen (23 patients out of 120) 5
- Flatulence (16 patients out of 120) 5
- Retching (13 patients out of 120) 5
- Dysgeusia (7 patients out of 120) 5
Management of Side Effects
To manage gastrointestinal side effects, patients can try temporary discontinuation, dose titration, or proper intake of medicine 5. Switching to an extended-release formulation of metformin may also reduce the frequency of gastrointestinal side effects 6. In cases of lactic acidosis, renal replacement therapy is the critical management option 4.