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Glucophage (metformin) Disease Interactions

There are 4 disease interactions with Glucophage (metformin):


Metformin (Includes Glucophage) ↔ Lactic Acidosis

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction, Liver Disease, Congestive Heart Failure, Dehydration, Shock, Myocardial Infarction, Asphyxia, Acidosis, Diarrhea, Vomiting, Anemia, Alcoholism

The use of metformin is contraindicated in patients with renal dysfunction (serum creatinine >= 1.5 mg/dL in males and 1.4 mg/dL in females, or above the upper limit of normal for age); congestive heart failure requiring pharmacologic treatment (especially unstable or acute CHF where there is risk of hypoperfusion and hypoxemia); and any condition associated with hypoxemia (e.g., severe anemia, myocardial infarction, asphyxia, shock), dehydration (e.g., severe diarrhea or vomiting), or sepsis. Patients with these conditions may be at increased risk for the development of lactic acidosis, which is a rare but serious metabolic complication associated with metformin accumulation in plasma usually at levels exceeding 5 mcg/mL. Metformin should also not be administered to patients with acute or chronic metabolic acidosis. In addition, metformin should generally be avoided in alcoholics and patients with clinical or laboratory evidence of hepatic disease, since alcohol potentiates the effects of metformin on lactate metabolism and impaired hepatic function may significantly limit the ability to clear lactate. All patients treated with metformin should have renal function monitored regularly (at least annually or more frequently if necessary) and be advised of the significance of nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and gastrointestinal disturbances that arise after stabilization of metformin dosage. More marked acidosis may be associated with hypothermia, hypotension, and resistant bradyarrhythmias. Immediate medical attention is necessary if these symptoms occur, and metformin therapy withheld until the situation can be clarified. If lactic acidosis is diagnosed, prompt supportive measures and hemodialysis are recommended.


  1. DeFronzo RA, Goodman AM, and the Multicenter Metformin Study Group "Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus." N Engl J Med 333 (1995): 541-9
  2. Misbin RI, Green L, Stadel BV, Gueriguian JL, Gubbi A, Fleming GA "Lactic acidosis in patients with diabetes treated with metformin." N Engl J Med 338 (1998): 265-6
  3. Lalau JD, Mourlhon C, Bergeret A, Lacroix C "Consequences of metformin intoxication." Diabetes Care 21 (1998): 2036-7
View all 21 references

Oral Hypoglycemic Agents (Includes Glucophage) ↔ Cardiovascular Risk

Severe Potential Hazard, Moderate plausibility

Applies to: Cardiovascular Disease

The use of oral hypoglycemic agents may be associated with an increased risk of cardiovascular mortality compared to treatment with diet alone or diet with insulin. This warning is based on the University Group Diabetes Program (UGDP) study, a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. Patients treated with diet plus a fixed dosage of either tolbutamide (a sulfonylurea) or phenformin (a biguanide) for 5 to 8 years had a cardiovascular mortality rate approximately 2.5 times that of patients treated with diet alone, resulting in discontinuation of both these treatments in the study. Despite controversy regarding interpretation of these results, clinicians and patients should be aware of the potential risk when making treatment decisions for diabetes, particularly in the presence of underlying cardiovascular disease. Data are not available for other sulfonylureas or biguanides, nor for hypoglycemic agents belonging to other classes. However, given the similarities in chemical structure and/or mode of action, the same caution should be applied.


  1. "Product Information. Glucotrol (glipizide)." Pfizer US Pharmaceuticals, New York, NY.
  2. "Product Information. Amaryl (glimepiride)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  3. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.
View all 8 references

Insulin/Oral Hypoglycemic Agents (Includes Glucophage) ↔ Hypoglycemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Adrenal Insufficiency, Malnourished, Autonomic Neuropathy, Panhypopituitarism, Anorexia/Feeding Problems

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.


  1. "Product Information. Glucotrol (glipizide)." Pfizer US Pharmaceuticals, New York, NY.
  2. Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL, eds. "Harrison's Principles of Internal Medicine. 14th ed." New York, NY: McGraw-Hill Health Professionals Division (1998):
  3. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb, Princeton, NJ.
View all 15 references

Metformin (Includes Glucophage) ↔ B12 Deficiency

Moderate Potential Hazard, Moderate plausibility

Applies to: Folic Acid/Cyanocobalamin Deficiency, Anemia Associated with Vitamin B12 Deficiency

Metformin may interfere with vitamin B12 (cyanocobalamin) absorption from the B12-intrinsic factor complex. A decrease to subnormal levels of previously normal serum B12 levels has been reported in approximately 7% of patients treated with metformin during controlled clinical trials. Although the decrease is generally well-tolerated and rarely associated with clinical manifestations such as megaloblastic anemia, caution may be warranted when metformin therapy is administered in patients with preexisting B12 deficiency. Vitamin B12 supplementation as well as annual measurements of hematologic parameters may be appropriate.


  1. Deutsch JC, Santhosh-Kumar CR, Kolhouse JF "Efficacy of metformin in non-insulin-dependent diabetes mellitus." N Engl J Med 334 (1996): 269
  2. Callaghan TS, Hadden DR, Tomkin GH "Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment." Br Med J 280 (1980): 1214-5
  3. Stowers JM, Smith OA "Vitamin B 12 and metformin." Br Med J 3 (1971): 246-7
View all 6 references

Glucophage (metformin) drug Interactions

There are 702 drug interactions with Glucophage (metformin)

Glucophage (metformin) alcohol/food Interactions

There is 1 alcohol/food interaction with Glucophage (metformin)

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No information available.

Do not stop taking any medications without consulting your healthcare provider.

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