Table 1. Adverse effects related to use of metformin.

Adapted from Kalantar-Zadeh K, Kovesdy CP: Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? No, We Should Never Again Compromise Safety! Diabetes care. 2016;39(7):1281–6.

Adverse Effect	Frequency	Comments
Lactic acidosis	Rare	Typically in the context of acute kidney injury, chronic kidney disease, and/or metformin overdose. High fatality rate in case series.
Hypoglycemia	Rare to moderate	More common with kidney dysfunction.
Pancreatitis	Rare	May be concurrent with lactic acidosis.
Mortality (independent of lactic acidosis)	Rare, but more common in kidney dysfunction	Recent Taiwanese historical study suggests 35% higher death risk in patients with Stage 5 chronic kidney disease (creatinine >6.0 mg/dl).
Cardiovascular toxicity	Rare to moderate	Guanidino compounds are known uremic toxins causing cardiovascular disease. Chest discomfort, flushing, and palpitations in up to 10% of patients. Worsening heart failure may be related to lactic acidosis or via independent mechanisms.
Hormonal derangements	Rare	Studies in fish show intersex fish and other anomalies.
Gastrointestinal	Common	Symptoms are usually mild, transient, and reversible after dose reduction or discontinuation of the drug: Metallic taste, anorexia, soft stools/diarrhea, nausea, vomiting, flatulence.
Vitamin B12 deficiency	Rare	Metformin reduces intestinal absorption of vitamin B12 in up to 30% of patients and lowers serum B12 level in 5–10% of patients. Rarely causes megaloblastic anemia.
Neurologic	Rare to moderate	Headache (6%), chills, dizziness, lightheadedness, myalgia, weakness, altered mental status.