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Glyburide / metformin Side Effects

Not all side effects for glyburide / metformin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to glyburide / metformin: oral tablet

In addition to its needed effects, some unwanted effects may be caused by glyburide / metformin. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking glyburide / metformin:

More common
  • Anxious feeling
  • behavior change similar to being drunk
  • blurred vision
  • cold sweats
  • confusion
  • convulsions (seizures)
  • cool pale skin
  • cough
  • difficulty in concentrating
  • drowsiness
  • excessive hunger
  • fast heartbeat
  • fever
  • headache (continuing)
  • nausea
  • nervousness
  • nightmares
  • restless sleep
  • shakiness
  • slurred speech
  • sneezing
  • sore throat
  • unconsciousness
  • unusual tiredness or weakness
  • Abdominal or stomach discomfort
  • decreased appetite
  • diarrhea
  • fast shallow breathing
  • general feeling of discomfort
  • muscle pain or cramping
  • unusual sleepiness

Some of the side effects that can occur with glyburide / metformin may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Dizziness
  • headache
  • vomiting

For Healthcare Professionals

Applies to glyburide / metformin: oral tablet


Metabolic side effects of metformin have included lactic acidosis, which is a potentially fatal metabolic complication of biguanide therapy. 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 glyburide's pharmacologic effects, has occurred 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.[Ref]

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 glyburide'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 glyburide 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.

Patients with renal dysfunction, liver disease, adrenal or pituitary insufficiency, or congestive heart failure may be at increased risk for hypoglycemia as are those who are elderly, debilitated, or malnourished. In addition, acute illness, lack of adherence to diet, ethanol ingestion, or strenuous exercise may precipitate hypoglycemia.[Ref]


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


Hematologic side effects of glyburide 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.[Ref]


Hepatic side effects of glyburide have included elevations in serum transaminase, alkaline phosphatase, and bilirubin, although jaundice has been only rarely reported. Elevations in liver function tests are usually mild and often return 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 glyburide use.

Postmarketing reports have included rare reports of cholestatic jaundice and hepatitis, some of which have progressed to liver failure. Glyburide-metformin should be discontinued if this occurs.[Ref]

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.[Ref]


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


Renal side effects of glyburide have included include polyuria and nocturia.[Ref]


Dermatologic side effects have included pruritus, erythema, urticaria, morbilliform and maculopapular eruptions, and vesiculobullous rash in 1.5% of patients who received glyburide occurred in clinical trials In addition, pemphigus vulgaris, porphyria cutanea tarda, Stevens-Johnson syndrome, and photosensitivity have been reported.[Ref]


Hypersensitivity side effects of glyburide have typically included dermatological effects but have also included acute hepatic hypersensitivity, cholestatic jaundice, necrotizing angiitis, hemolytic anemia, angioedema, arthralgia, myalgia, and vasculitis.[Ref]


Ocular side effects of glyburide have included changes in accommodation and blurred vision.[Ref]


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