Skip to Content
Reach blood sugar goals with long-acting insulin. Go >

Metformin / pioglitazone Disease Interactions

There are 13 disease interactions with metformin / pioglitazone:

Major

Metformin (Includes Metformin/pioglitazone) ↔ Lactic Acidosis

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction, Liver Disease, Congestive Heart Failure, Dehydration, Sepsis, 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.

References

  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
Major

Oral Hypoglycemic Agents (Includes Metformin/pioglitazone) ↔ 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.

References

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

Thiazolidinediones (Includes Metformin/pioglitazone) ↔ Chf

Severe Potential Hazard, Moderate plausibility

Applies to: Congestive Heart Failure

The use of thiazolidinediones, alone or in combination with other antidiabetic agents, has been associated with fluid retention and new onset or exacerbation of heart failure. An increased risk of cardiovascular events (heart failure worsening; new or worsening edema; new or worsening dyspnea; increases in heart failure medication; myocardial infarction; angina; cardiovascular hospitalization and deaths) has been reported with rosiglitazone therapy in type II diabetic patients with New York Heart Association (NYHA) Class I or II congestive heart failure compared to placebo. Likewise, overnight hospitalization for CHF was observed in 9.9% of diabetic patients with NYHA Class II and III heart failure on pioglitazone compared to 4.7% of patients on glyburide. An increased incidence of cardiovascular adverse events including edema and cardiac failure has also been reported in patients receiving a thiazolidinedione in combination with insulin relative to insulin and placebo. Therapy with thiazolidinediones should be administered cautiously and initiated at the lowest recommended dosage in patients with congestive heart failure. Thiazolidinediones are contraindicated for the treatment of patients with NYHA Class III or IV cardiac status. Patients should be monitored for signs of worsening heart failure such as increased dyspnea, edema, and weight gain. Therapy should be discontinued if any deterioration in cardiac status occurs.

References

  1. "Product Information. Avandia (rosiglitazone)" SmithKline Beecham, Philadelphia, PA.
  2. "Product Information. Actos (pioglitazone)" Takeda Pharmaceuticals America, Lincolnshire, IL.
Moderate

Insulin/Oral Hypoglycemic Agents (Includes Metformin/pioglitazone) ↔ 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.

References

  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
Moderate

Metformin (Includes Metformin/pioglitazone) ↔ 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.

References

  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
Moderate

Pioglitazone (Includes Metformin/pioglitazone) ↔ Bladder Cancer

Moderate Potential Hazard, Moderate plausibility

Applies to: Bladder Cancer

There are insufficient data to determine if pioglitazone has an effect on preexisting bladder tumors or if it can cause bladder cancer. However, the manufacturer does not recommend the use of pioglitazone in patients with active bladder cancer. In patients with history of bladder cancer the benefit of treatment versus the risk of cancer recurrence during treatment should be considered.

Moderate

Thiazolidinediones (Includes Metformin/pioglitazone) ↔ Edema

Moderate Potential Hazard, Moderate plausibility

Applies to: Hypertension, Pleural Effusion, Pulmonary Edema, Fluid Retention

Thiazolidinediones can cause dose-related edema. Therapy with thiazolidinediones should be administered cautiously in patients at risk for congestive heart failure as well as those with fluid overload or other conditions that may be adversely affected by excess fluid such as hypertension. Patients should be monitored for signs and symptoms of heart failure such as dyspnea, swelling of legs or ankles, and weight gain.

References

  1. "Product Information. Rezulin (troglitazone)." Parke-Davis, Morris Plains, NJ.
  2. "Product Information. Avandia (rosiglitazone)" SmithKline Beecham, Philadelphia, PA.
  3. "Product Information. Actos (pioglitazone)" Takeda Pharmaceuticals America, Lincolnshire, IL.
View all 4 references
Moderate

Thiazolidinediones (Includes Metformin/pioglitazone) ↔ Liver Disease

Moderate Potential Hazard, Moderate plausibility

Applies to: Liver Disease

Initiation of rosiglitazone or pioglitazone therapy is not recommended in patients who exhibit clinical evidence of active liver disease or increased baseline serum transaminase levels (ALT exceeding 2.5 times upper limit of normal). Use of these agents is also not recommended in patients who have experienced jaundice during treatment with troglitazone. The use of troglitazone, another agent in the thiazolidinedione class, has been associated with clinically significant elevations in liver enzymes, reversible jaundice, and idiosyncratic hepatocellular injury including rare cases of liver failure, liver transplants, and death. Injury has occurred after both short- and long-term treatment. While these effects have not been associated with other thiazolidinediones in clinical trials, concerns exist because of their structural similarities. In addition, isolated cases of hepatitis and hepatic enzyme elevations to 3 or more times the upper limit of normal have been reported with both rosiglitazone and pioglitazone during postmarketing use. Rarely, these events have involved hepatic failure with and without fatal outcome, although causality has not been established. Until more safety data are available, patients who are prescribed thiazolidinedione therapy should have serum transaminase levels checked at baseline and periodically thereafter as clinically necessary. Mild to moderate elevations (ALT less than or equal to 2.5 times ULN) require cautious use with more frequent monitoring to determine if the elevations resolve or worsen. Patients who develop potential symptoms of hepatic injury such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, and dark urine should have liver enzymes checked. Therapy should be withdrawn if ALT is elevated and persists above 3 times ULN or if jaundice develops.

References

  1. "Product Information. Avandia (rosiglitazone)" SmithKline Beecham, Philadelphia, PA.
  2. Gitlin N, Julie NL, Spurr CL, Lim KN, Juarbe HM "Two cases of severe clinical and histologic hepatotoxicity associated with troglitazone." Ann Intern Med 129 (1998): 36-8
  3. Watkins PB, Whitcomb RW "Hepatic dysfunction associated with troglitazone." N Engl J Med 338 (1998): 916-7
View all 11 references
Moderate

Thiazolidinediones (Includes Metformin/pioglitazone) ↔ Macular Edema

Moderate Potential Hazard, Moderate plausibility

Applies to: Macular Edema, Diabetes Mellitus

New onset or worsening diabetic macular edema with decreased visual acuity have been reported in postmarketing reports in some diabetic patients who were taking thiazolidinedione drugs. Some patients presented with blurred vision or decreased visual acuity, but some patients appear to have been diagnosed on routine ophthalmologic examination. Most patients had peripheral edema at the time macular edema was diagnosed. Some patients had improvement in their macular edema after discontinuation of their thiazolidinedione. Patients with diabetes should have regular eye exams by an ophthalmologist according to current standards of care. Additionally, any diabetic who reports any kind of visual symptom should be promptly referred to an ophthalmologist, regardless of the patient's underlying medications or other physical findings.

Moderate

Thiazolidinediones (Includes Metformin/pioglitazone) ↔ Premenopausal Anovulation

Moderate Potential Hazard, Moderate plausibility

Applies to: Premenopausal Anovulation

In premenopausal, anovulatory patients with insulin resistance, treatment with thiazolidinediones may result in resumption of ovulation. Due to improved insulin sensitivity, pregnancy can occur if adequate contraception is not used.

References

  1. "Product Information. Rezulin (troglitazone)." Parke-Davis, Morris Plains, NJ.
  2. "Product Information. Actos (pioglitazone)" Takeda Pharmaceuticals America, Lincolnshire, IL.
  3. "Product Information. Avandia (rosiglitazone)" SmithKline Beecham, Philadelphia, PA.
Moderate

Thiazolidinediones (Includes Metformin/pioglitazone) ↔ Type I Diabetes

Moderate Potential Hazard, Moderate plausibility

Applies to: Diabetic Ketoacidosis, Diabetes Type 1

Thiazolidinediones exert their hypoglycemic effect only in the presence of insulin. Therefore, these agents should not be used in patients with type I diabetes or for the treatment of diabetic ketoacidosis.

References

  1. "Product Information. Avandia (rosiglitazone)" SmithKline Beecham, Philadelphia, PA.
  2. "Product Information. Actos (pioglitazone)" Takeda Pharmaceuticals America, Lincolnshire, IL.
Moderate

Thiazolidinediones (Includes Metformin/pioglitazone) ↔ Weight Gain

Moderate Potential Hazard, Moderate plausibility

Applies to: Obesity

Thiazolidinediones can cause dose-related weight gain, which may be undesirable in obese patients attempting to lose weight. The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation. In postmarketing experience with rosiglitazone, there have been reports of unusually rapid increases in weight, greater than those generally observed in clinical trials. Patients who experience such increases should be assessed for fluid retention and volume-related events such as excessive edema and congestive heart failure.

References

  1. "Product Information. Actos (pioglitazone)" Takeda Pharmaceuticals America, Lincolnshire, IL.
  2. "Product Information. Avandia (rosiglitazone)" SmithKline Beecham, Philadelphia, PA.
Moderate

Thiazolidinediones (Includes Metformin/pioglitazone) ↔ Anemia

Minor Potential Hazard, Moderate plausibility

Applies to: Anemia

Thiazolidinediones can cause slight decreases in hemoglobin and hematocrit. In clinical studies, hemoglobin levels were reduced primarily within the first 4 to 12 weeks of therapy but remained relatively constant thereafter. These changes may be related to increased plasma volume and have rarely been associated with any significant hematologic clinical effects. Nevertheless, caution may be advisable when thiazolidinediones are prescribed to patients with certain anemias.

References

  1. "Product Information. Avandia (rosiglitazone)" SmithKline Beecham, Philadelphia, PA.
  2. "Product Information. Actos (pioglitazone)" Takeda Pharmaceuticals America, Lincolnshire, IL.

metformin / pioglitazone drug Interactions

There are 747 drug interactions with metformin / pioglitazone

metformin / pioglitazone alcohol/food Interactions

There are 3 alcohol/food interactions with metformin / pioglitazone

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.

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

Disclaimer: Every effort has been made to ensure that the information provided by Multum is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. Multum's information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill, knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective, or appropriate for any given patient. Multum Information Services, Inc. does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. Copyright 2000-2016 Multum Information Services, Inc. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.

Hide