What are the adverse side effects of Metformin (biguanide oral hypoglycemic)

From the Guidelines

Metformin can cause several adverse side effects, including gastrointestinal issues, vitamin B12 deficiency, and lactic acidosis, and its use should be carefully monitored, especially in patients with kidney dysfunction or other comorbidities, as recommended by the most recent guidelines 1.

Common Side Effects

• Gastrointestinal issues such as nausea, vomiting, diarrhea, abdominal discomfort, and a metallic taste in the mouth, which affect approximately 30% of patients
• These digestive symptoms typically occur when starting the medication and often improve over time
• To minimize these effects, metformin should be taken with meals and started at a low dose (500 mg once or twice daily) before gradually increasing to the target dose (typically 1000-2000 mg daily)

Less Common but Serious Side Effects

• Vitamin B12 deficiency can develop with long-term use, so periodic monitoring of B12 levels is recommended, especially in elderly patients or those with poor nutrition
• Lactic acidosis is a rare but serious side effect with symptoms including muscle pain, difficulty breathing, unusual sleepiness, and stomach discomfort
• This complication occurs primarily in patients with kidney dysfunction, liver disease, or during acute illness, which is why metformin is contraindicated in patients with significant renal impairment (eGFR <30 mL/min)

Special Considerations

• Metformin may be used safely in individuals with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², while lower doses may be used in those with an eGFR 30–45 mL/min/1.73 m² 1
• Metformin should be discontinued in patients presenting with acute conditions associated with lactic acidosis, such as cardiogenic or distributive shock 1
• Patients should be aware that certain conditions like dehydration, excessive alcohol intake, or contrast dye procedures can increase the risk of side effects and may require temporary discontinuation of the medication 1

From the FDA Drug Label

Lactic acidosis Metformin, the active ingredient in metformin hydrochloride tablets, can cause a rare but serious condition called lactic acidosis (a buildup of an 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.

The adverse side effects of Metformin include:

• Lactic Acidosis: a rare but serious condition that can cause death
• Gastrointestinal symptoms:
  • Diarrhea
  • Nausea
  • Upset stomach
• Metallic taste: an unpleasant taste experienced by about 3 out of every 100 people
• Hypoglycemia: low blood sugar, which rarely occurs by itself but can happen if the patient does not eat enough, drinks alcohol, or takes other medicines to lower blood sugar 2 Other adverse reactions reported in clinical trials include:
• Asthenia
• Flatulence
• Indigestion
• Abdominal discomfort
• Headache
• Abnormal stools
• Hypoglycemia
• Myalgia
• Lightheadedness
• Dyspnea
• Nail disorder
• Rash
• Sweating increased
• Taste disorder
• Chest discomfort
• Chills
• Flu syndrome
• Flushing
• Palpitation 2

From the Research

Adverse Side Effects of Metformin

The adverse side effects of Metformin, a biguanide oral hypoglycemic, include:

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Anorexia 3
• Lactic acidosis, a serious side effect that can be life-threatening 3, 4, 5
• Gastrointestinal symptoms such as severe abdominal pain and nausea 4
• Flatulence, indigestion, and abdominal discomfort 6

Risk Factors for Adverse Side Effects

Certain risk factors can increase the likelihood of adverse side effects from Metformin, including:

• Cardiovascular, pulmonary, and renal and liver failure 3
• Kidney and liver conditions, malignancy, or use of certain medications 4
• Acute kidney injury (AKI) 4
• Alcoholic liver disease 5
• Renal dysfunction 4

Management of Adverse Side Effects

To manage adverse side effects, the following strategies can be employed:

• Starting at a low dose and titrating slowly 6
• Using extended-release metformin instead of immediate-release metformin 7, 6
• Considering alternative pharmacological therapies when metformin cannot be tolerated 6
• Prompt treatment of lactic acidosis with intravenous fluids and bicarbonate drip 4