From the Guidelines
The most common side effects of metformin are gastrointestinal intolerance, including bloating, abdominal discomfort, and diarrhea, which can be mitigated by gradual dose titration and/or using extended-release formulation. These side effects are typically temporary and improve after a few weeks as the body adjusts to the medication. According to the most recent study 1, metformin is effective and safe, and its principal side effects are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea. To minimize these effects, metformin should be taken with meals and started at a low dose before gradually increasing to the target dose.
- Other common side effects include: + Decreased vitamin B12 levels with long-term use, which may require monitoring and supplementation 1 + Lactic acidosis, a rare but serious side effect, occurring primarily in patients with kidney dysfunction, liver disease, or during acute illness 1, 2
- The medication works by reducing glucose production in the liver and improving insulin sensitivity in muscle and fat tissues, which explains why gastrointestinal effects are common as the medication interacts with cells in the digestive tract.
- It is essential to note that metformin may accumulate with reduced kidney function and may increase the risk for lactic acidosis, although this risk is very low in absolute terms 2.
- Patients receiving metformin should have their estimated glomerular filtration rate (eGFR) monitored, and the dose should be reduced when the eGFR is less than 45 mL/min/1.73 m2 or withdrawn when the eGFR is less than 30 mL/min/1.73 m2 or kidney failure develops 2.
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 Tablets Occurring >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 most common side effects of metformin are:
- Diarrhea: 53% of patients
- Nausea/Vomiting: 26% of patients
- Flatulence: 12% of patients
- Asthenia: 9% of patients
- Indigestion: 7% of patients
- Abdominal Discomfort: 6% of patients
- Headache: 6% of patients These side effects generally go away after taking the medicine for a while, and taking the medicine with meals can help reduce these side effects 3.
From the Research
Common Side Effects of Metformin
The most common side effects of metformin include:
- Diarrhoea
- Nausea
- Flatulence
- Indigestion
- Vomiting
- Abdominal discomfort
- Abdominal pain
- Bloating
Comparison of Side Effects
Studies have shown that the risk of gastrointestinal adverse events such as abdominal pain, nausea, and diarrhea is higher in type 2 diabetes patients treated with metformin compared to other antidiabetic drugs 4, 5. Additionally, the risk of bloating and diarrhea is higher with metformin immediate-release than with metformin extended-release formulation 5.
Management of Side Effects
Starting at a low dose and titrating slowly may help prevent some gastrointestinal adverse events associated with metformin 4. Other strategies to overcome metformin gastrointestinal intolerance include the use of extended-release metformin, delayed-release metformin, and gut microbiome modulators 4.
Note: The study 6 is not relevant to the question about metformin side effects, as it discusses the clinical trial of weekly pyrazofurin.