Signs and symptoms of severe acidosis may include vomiting, abdominal pain, nausea, dyspnea (difficulty breathing), hypothermia, hypotension, and bradycardia. (dropping body temperature, blood pressure and heart rate)

Laboratory evaluation of metformin-induced lactic acidosis generally includes determination of the following: blood glucose concentration, lactic acid concentration, serum electrolytes, blood pH, metformin concentration, and exclusion of ketoacidosis.

If lactic acidosis is present, immediate institution of general supportive care is indicated. Prompt hemodialysis (cleaning your blood for your kidneys)  is also generally recommended in order to correct the acidosis and remove metformin. Hemodialysis often results in rapid improvement. Some investigators have suggested that dialysis with a bicarbonate-buffered dialysate may be particularly effective.

Metabolic side effects have included lactic acidosis, which is a potentially fatal metabolic complication. The incidence of lactic acidosis has been about 1.5 cases per 10,000 patient years. The risk of lactic acidosis has been particularly high in patients with underlying renal insufficiency. Cases of lactic acidosis occurring in patients with normal renal function have been rarely reported. Concomitant cardiovascular or liver disease, sepsis, and hypoxia have also increased the risk of lactic acidosis.

Subnormal vitamin B12 levels have been reported, and may result in anemia or neuropathy (diseased condition of the nervous system). Serum vitamin B12 levels at 2 to 3 year intervals may be useful.

Hypoglycemia (low blood sugar) occurred uncommonly in patients receiving metformin as monotherapy. Strenuous exercise, decreased caloric intake, general debilitation, adrenal insufficiency, pituitary insufficiency, and ethanol use have increased the risk of hypoglycemia.  (low blood sugar)

Gastrointestinal Side Effects

Gastrointestinal effects have included nausea, anorexia, metallic taste, diarrhea, dyspepsia (indigestion or upset stomach), flatulence, and abdominal pain. One study has reported a 20% incidence of diarrhea.

Hematologic Side Effects

Hematologic (involving your blood) side effects have included malabsorption of vitamin B12, due to intrinsic factor deficiency and possibly other mechanisms, in as many as 30% of treated patients. Megaloblastic anemia has occurred. Discontinuation of metformin or supplementation with vitamin B12 has been necessary.

Other Side Effects

Other side effects include a single case of leukocytoclastic vasculitis with pneumonitis.  (Serious disease of the blood and lungs!)

Hepatic Side Effects

Hepatic side effects have included at least two cases of hepatitis (inflammation of the liver) associated with metformin use.

A 52-year-old female with a history of type II diabetes mellitus and hypertension developed lethargy, fatigue, and diarrhea after taking metformin for more than 2 weeks. After continuing metformin for a total of four weeks, her sclera became icteric and she was hospitalized. Aside from a soft systolic ejection fracture and a moderate degree of bilateral lower extremity edema, her physical examination was unremarkable. Laboratory data showed grossly elevated total bilirubin, AST, ALT, and alkaline phosphatase. Several days after her initial presentation all of her medications were discontinued. Her signs and symptoms significantly improved over the following several days, and she was discharged within two weeks of her hospitalization. The patient’s presentation was considered consistent with drug-induced toxicity attributed to metformin.

Article originally posted on Drugs.com.