Skip to main content

Metformin Disease Interactions

There are 4 disease interactions with metformin.


Metformin (applies to metformin) lactic acidosis

Major Potential Hazard, High plausibility. Applicable conditions: Renal Dysfunction, Liver Disease, Congestive Heart Failure, Dehydration, Shock, Myocardial Infarction, Asphyxia, 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. Chalopin JM, Tanter Y, Besancenot JF, Cabanne JF, Rifle G "Treatment of metformin-associated lactic acidosis with closed recirculation bicarbonate-buffered hemodialysis." Arch Intern Med 144 (1984): 203-5
  2. Biron P "Metformin monitoring." Can Med Assoc J 123 (1980): 11-2
  3. Ryder RE "Lactic acidotic coma with multiple medication including metformin in a patient with normal renal function." Br J Clin Pract 38 (1984): 229-30,232
  4. Luft D, Schmulling RM, Eggstein M "Lactic acidosis in biguanide-treated diabetics: a review of 330 cases." Diabetologia 14 (1978): 75-87
  5. Assan R, Heuclin C, Ganeval D, Bismuth C, George J, Girard JR "Metformin-induced lactic acidosis in the presence of acute renal failure." Diabetologia 13 (1977): 211-7
  6. Wiholm BE, Myrhed M "Metformin-associated lactic acidosis in Sweden 1977-1991." Eur J Clin Pharmacol 44 (1993): 589-91
  7. Lalau JD, Andrejak M, Moriniere P, Coevoet B, Debussche X, Westeel PF, Fournier A, Quichaud J "Hemodialysis in the treatment of lactic acidosis in diabetics treated by metformin: a study of metformin elimination." Int J Clin Pharmacol Ther Toxicol 27 (1989): 285-8
  8. Lalau JD, Westeel PF, Debussche X, Dkissi H, Tolani M, Coevoet B, Temperville B, Fournier A, Quichaud J "Bicarbonate haemodialysis: an adequate treatment for lactic acidosis in diabetics treated by metformin." Intensive Care Med 13 (1987): 383-7
  9. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb (2001):
  10. 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
  11. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE "Metabolic effects of metformin in non-insulin-dependent diabetes mellitus." N Engl J Med 333 (1995): 550-4
  12. Sambol NC, Chiang J, Lin ET, Goodman AM, Liu CY, Benet LZ, Cogan MG "Kidney function and age are both predictors of pharmacokinetics of metformin." J Clin Pharmacol 35 (1995): 1094-102
  13. Gueriguian J, Green L, Misbin RI, Stadel B, Fleming GA "Efficacy of metformin in non-insulin dependent diabetes mellitus." N Engl J Med 334 (1996): 269
  14. De Fronzo RA, Goodman AM "Efficacy of metformin in non-insulin dependent diabetes mellitus." N Engl J Med 334 (1996): 269-70
  15. Deutsch JC, Santhoshkumar CR, Kolhouse JF "Efficacy of metformin in non-insulin-dependent diabetes mellitus." N Engl J Med 334 (1996): 269
  16. Bailey CJ, Path MR, Turner RC "Metformin." N Engl J Med 334 (1996): 574-9
  17. Pearlman BL, Fenves AZ, Emmett M "Metformin-associated lactic acidosis." Am J Med 101 (1996): 109-10
  18. Lustik SJ, Vogt A, Chhibber AK "Postoperative lactic acidosis in patients receiving metformin." Anesthesiology 89 (1998): 266-7
  19. Lalau JD, Mourlhon C, Bergeret A, Lacroix C "Consequences of metformin intoxication." Diabetes Care 21 (1998): 2036-7
  20. 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
  21. Stang M, Wysowski DK, ButlerJones D "Incidence of lactic acidosis in metformin users." Diabetes Care 22 (1999): 925-7
View all 21 references

Oral hypoglycemic agents (applies to metformin) cardiovascular risk

Major Potential Hazard, Moderate plausibility. Applicable conditions: 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. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals (2002):
  2. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals (2002):
  3. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb (2001):
  5. "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel (2001):
  6. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc (2001):
  7. "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn (2001):
  8. "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn (2001):
  9. "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company (2001):
View all 9 references

Insulin/oral hypoglycemic agents (applies to metformin) hypoglycemia

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: 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. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals (2002):
  2. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals (2002):
  3. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. "Product Information. Micronase (glyburide)." Pharmacia and Upjohn (2002):
  5. "Multum Information Services, Inc. Expert Review Panel"
  6. "Product Information. Humulin BR (insulin)." Lilly, Eli and Company, Indianapolis, IN.
  7. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb (2001):
  8. "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel (2001):
  9. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc (2001):
  10. Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division (1998):
  11. "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn (2001):
  12. "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company (2001):
  13. "Product Information. Lantus (insulin glargine)." Aventis Pharmaceuticals (2001):
  14. "Product Information. NovoLOG (insulin aspart)." Novo Nordisk Pharmaceuticals Inc (2022):
  15. "Product Information. Starlix (nateglinide)." Novartis Pharmaceuticals (2001):
  16. "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals (2004):
  17. "Product Information. Levemir (insulin detemir)." Novo Nordisk Pharmaceuticals Inc (2005):
  18. "Product Information. Tresiba FlexTouch (insulin degludec)." Novo Nordisk Pharmaceuticals Inc (2015):
View all 18 references

Metformin (applies to metformin) B12 deficiency

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: 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. Tomkin GH "Metformin and B 12 malabsorption." Ann Intern Med 76 (1972): 668
  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
  4. Tomkin GH, Hadden DR, Weaver JA, Montgomery DA "Vitamin-B12 status of patients on long-term metformin therapy." Br Med J 2 (1971): 685-7
  5. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb (2001):
  6. Deutsch JC, Santhosh-Kumar CR, Kolhouse JF "Efficacy of metformin in non-insulin-dependent diabetes mellitus." N Engl J Med 334 (1996): 269
View all 6 references

Metformin drug interactions

There are 359 drug interactions with metformin.

Metformin alcohol/food interactions

There is 1 alcohol/food interaction with metformin.

Report options

QR code containing a link to this page

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
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 interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.