Glipizide/Metformin Side Effects

Please note - some side effects for Glipizide/Metformin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Glipizide/Metformin - for the Consumer

Glipizide/Metformin

All medicines may cause side effects, but many people have no, or minor side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Glipizide/Metformin:

Diarrhea; headache; indigestion; mild stomach pain; nausea; stomach upset; vomiting.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain or discomfort; confusion; dizziness or lightheadedness; fainting; fast or difficult breathing; feeling of being unusually cold; fever, chills, or persistent sore throat; general feeling of being unwell; low blood sugar symptoms (eg, anxiety, dizziness, fast heartbeat, headache, tremors, unusual sweating); muscle pain or weakness; severe or persistent blurred vision or other vision problems; slow or irregular heartbeat; unusual drowsiness; unusual or persistent stomach pain or discomfort; unusual tiredness or weakness.

Side Effects by Body System

Metabolic

Metabolic side effects, including lactic acidosis, which is a potentially fatal metabolic complication of biguanide therapy, has been reported in patients receiving metformin. The incidence of lactic acidosis has been about 0.03 cases per 1,000 patient years with approximately 0.015 fatal cases per 1,000 patient-years. The risk of lactic acidosis is 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 may also increase the risk of lactic acidosis.

Hypoglycemia, an extension of glipizide's pharmacologic effects, occurs in 1.6% to 3.1% of patients. Hypoglycemia may be severe and protracted. Strenuous exercise, decreased caloric intake, general debilitation, adrenal insufficiency, pituitary insufficiency, and ethanol use may increase the risk of hypoglycemia. Fatalities are reported. In addition, hyponatremia and disulfiram-like reactions are reported.

Lactic acidosis is a medical emergency requiring immediate evaluation and treatment. The case fatality rate may be as high as 50%. Patients taking metformin who present with even vague medical illnesses such as myalgia, malaise, somnolence, abdominal discomfort, and so forth, should be evaluated for a metabolic etiology like lactic acidosis.

Signs and symptoms of severe acidosis may include vomiting, abdominal pain, nausea, dyspnea, hypothermia, hypotension, and bradycardia.

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 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.

Hypoglycemia, an extension of glipizide's pharmacologic effects, may be severe, protracted, refractory to glucose infusion, and, in some cases, may require diazoxide. It most commonly presents as coma or disturbed consciousness. Other signs of hypoglycemia include tachycardia, tremor, chest pain, weakness, and increased sweating. In one review of 57 spontaneously reported cases, the mean dose of glipizide associated with hypoglycemia was 10 mg per day although there were cases with doses as low as 2.5 mg per day. The median age in these cases was 75 years. Ten patients died. In another review of 13 cases, in which renal failure, advanced age, and congestive heart failure were deemed to be predisposing factors, hypoglycemia persisted for more than 60 hours in two patients.

Gastrointestinal

Gastrointestinal side effects of metformin have included nausea, anorexia, metallic taste, diarrhea, dyspepsia, flatulence, nausea, vomiting and abdominal pain. One study has reported a 20% incidence of diarrhea.

Hematologic

Hematologic side effects of glipizide have included rare reports of leukopenia, thrombocytopenia, eosinophilia, and hemolytic anemia.

Malabsorption of vitamin B12, due to intrinsic factor deficiency and possibly other mechanisms, has been reported in as many as 30% of patients treated with metformin. Megaloblastic anemia has occurred. Discontinuation of metformin or supplementation with vitamin B12 may be necessary.

Hepatic

Hepatic side effects of glipizide have included elevations in serum transaminase, alkaline phosphatase, and bilirubin, although jaundice is only rarely reported. Elevations in liver function tests were usually mild and often returned to normal despite continued therapy. Rare cases of acute hepatic hypersensitivity characterized by pruritus, icterus, and cholestatic jaundice have also been reported. In addition, at least two cases of granulomatous hepatitis have been associated with glipizide use.

At least two cases of hepatitis have been associated with metformin use.

Other

A single case of leukocytoclastic vasculitis with pneumonitis has been reported in association with metformin therapy.

Renal

Renal side effects of glipizide have included polyuria and nocturia.

Dermatologic

Dermatologic side effects in patients receiving glipizide have included pruritus, erythema, urticaria, morbilliform and maculopapular eruptions, and vesiculobullous rash. In addition, pemphigus vulgaris, porphyria cutanea tarda, Stevens-Johnson syndrome, and photosensitivity have been reported.

Hypersensitivity

Hypersensitivity reactions to glipizide have typically included dermatological effects but have also included acute hepatic hypersensitivity, cholestatic jaundice, necrotizing angiitis, hemolytic anemia, angioedema, arthralgia, myalgia, and vasculitis.

Ocular

Ocular side effects of glipizide have included changes in accommodation and blurred vision.

Respiratory

Respiratory side effects have included upper respiratory infections.

Genitourinary

Genitourinary side effects have included urinary tract infections.

Cardiovascular

Cardiovascular side effects have included hypertension.

Nervous system

Nervous system side effects have included headache and dizziness.

Musculoskeletal

Musculoskeletal side effects have included musculoskeletal pain.

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