Glucophage 500mg Tablets
WARNING: Rarely, metformin may cause too much lactic acid in the blood (lactic acidosis). The risk is higher in people who have kidney problems, liver problems, heart failure, use alcohol, or take certain other drugs, including topiramate. The risk is also higher in people who are 65 or older and in people who are having surgery, an exam or test with contrast, or other procedures. If lactic acidosis happens, it can lead to other health problems and can be deadly. Kidney tests may be done while taking this drug.Do not take this drug if you have a very bad infection, low oxygen, or a lot of fluid loss (dehydration).Call your doctor right away if you have signs of too much lactic acid in the blood (lactic acidosis) like confusion; fast breathing; fast or slow heartbeat; a heartbeat that does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; feeling very tired or weak; very bad dizziness; feeling cold; or muscle pain or cramps. @ COMMON USES: It is used to lower blood sugar in patients with high blood sugar (diabetes).
Drug Class
Antidiabetic
Pharmacologic Class
Biguanide
Pregnancy Category
Not available
FDA Approved
Dec 1995
DEA Schedule
Not Controlled
Overview
What is this medicine?
Metformin is a medication used to help control high blood sugar (glucose) levels in people with type 2 diabetes. It works by helping your body use insulin more effectively, reducing the amount of sugar your liver makes, and decreasing the amount of sugar your body absorbs from food. It's often the first medicine prescribed for type 2 diabetes.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. It's recommended to take this medication with meals.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better. It's essential to complete the full course of treatment as advised.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication, store it at room temperature, protected from light. Keep it in a dry place, avoiding storage in a bathroom. Ensure that all medications are kept in a secure location, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, skip it and resume your regular dosing schedule unless your doctor provides alternative instructions. Do not take two doses at the same time or take extra doses to make up for the missed one.
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. It's recommended to take this medication with meals.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better. It's essential to complete the full course of treatment as advised.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication, store it at room temperature, protected from light. Keep it in a dry place, avoiding storage in a bathroom. Ensure that all medications are kept in a secure location, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, skip it and resume your regular dosing schedule unless your doctor provides alternative instructions. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take metformin with meals to reduce stomach upset (nausea, diarrhea).
- Follow a healthy diet plan recommended by your doctor or dietitian.
- Engage in regular physical activity as advised by your healthcare provider.
- Limit alcohol intake, as excessive alcohol can increase the risk of a serious side effect called lactic acidosis.
- Stay well-hydrated, especially during exercise or in hot weather.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 500 mg orally twice daily or 850 mg orally once daily with meals. Titrate gradually. Maintenance: 850 mg orally twice daily or 1000 mg orally twice daily. Max: 2550 mg/day (immediate release).
Dose Range:
500 - 2550 mg
Condition-Specific Dosing:
Type 2 Diabetes Mellitus:
Initial: 500 mg BID or 850 mg QD. Increase by 500 mg weekly or 850 mg every 2 weeks as tolerated. Max: 2550 mg/day (IR) or 2000-2500 mg/day (ER).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established for <10 years. For 10-16 years: Initial 500 mg orally twice daily with meals. Increase by 500 mg weekly as tolerated. Max: 2000 mg/day.
Adolescent:
For 10-16 years: Initial 500 mg orally twice daily with meals. Increase by 500 mg weekly as tolerated. Max: 2000 mg/day.
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60-89 mL/min/1.73m²: No dose adjustment needed. Monitor eGFR annually.
Moderate:
eGFR 45-59 mL/min/1.73m²: Initial dose should not exceed 1000 mg/day. Max dose 2000 mg/day. Monitor eGFR every 3-6 months. eGFR 30-44 mL/min/1.73m²: Not recommended to initiate. If already on metformin, reduce dose by 50% (e.g., max 1000 mg/day) and monitor eGFR every 3 months. Discontinue if eGFR falls below 30 mL/min/1.73m².
Severe:
eGFR < 30 mL/min/1.73m²: Contraindicated.
Dialysis:
Contraindicated in patients with end-stage renal disease (ESRD) or on dialysis due to increased risk of lactic acidosis.
Hepatic Impairment:
Mild:
No specific adjustment, but use with caution.
Moderate:
Use with caution. Increased risk of lactic acidosis.
Severe:
Contraindicated due to increased risk of lactic acidosis.
Pharmacology
Mechanism of Action
Metformin is a biguanide that improves glycemic control by decreasing hepatic glucose production (gluconeogenesis), decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. It does not stimulate insulin secretion and therefore does not cause hypoglycemia when used as monotherapy.
Pharmacokinetics
Absorption:
Bioavailability:
50-60%
Tmax:
2-2.5 hours (immediate release); 4-8 hours (extended release)
FoodEffect:
Food decreases the extent and slightly delays the absorption of metformin.
Distribution:
Vd:
654 L (average)
ProteinBinding:
<5%
CnssPenetration:
Limited
Elimination:
HalfLife:
6.2 hours (plasma); 17.6 hours (blood)
Clearance:
Approximately 400 mL/min (renal clearance is 3.5 times greater than creatinine clearance)
ExcretionRoute:
Renal (primarily via tubular secretion)
Unchanged:
>90%
Pharmacodynamics
OnsetOfAction:
Days to weeks for full glucose-lowering effect
PeakEffect:
Variable, typically within 2-3 weeks of stable dosing
DurationOfAction:
Approximately 12 hours (immediate release)
Safety & Warnings
BLACK BOX WARNING
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal distress. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels generally >5 mcg/mL. If metformin-associated lactic acidosis is suspected, discontinue Glucophage immediately and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. Risk factors include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors), age 65 years or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Stomach problems that occur later during treatment, as they may be a sign of lactic acidosis (an acid health problem in the blood)
Low blood sugar symptoms, which may include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
If you experience low blood sugar, follow your doctor's instructions for treatment, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. Contact your doctor or seek medical help if you experience any of the following side effects or if they bother you or do not go away:
Stomach pain or heartburn
Gas
Diarrhea, upset stomach, or vomiting
Feeling tired or weak
Headache
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Stomach problems that occur later during treatment, as they may be a sign of lactic acidosis (an acid health problem in the blood)
Low blood sugar symptoms, which may include:
+ Dizziness
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
If you experience low blood sugar, follow your doctor's instructions for treatment, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. Contact your doctor or seek medical help if you experience any of the following side effects or if they bother you or do not go away:
Stomach pain or heartburn
Gas
Diarrhea, upset stomach, or vomiting
Feeling tired or weak
Headache
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Unusual muscle pain (myalgia)
- Feeling cold (hypothermia)
- Feeling very tired or weak (malaise, somnolence)
- Trouble breathing (respiratory distress)
- Stomach pain, nausea, or vomiting
- Dizziness or lightheadedness
- Slow or irregular heartbeat
- Unexplained weight loss (may indicate B12 deficiency)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
Recent medical events, such as a heart attack or stroke
Any difficulties with eating or drinking, including situations where you may be required to fast before a procedure or surgery
Additionally, if you are scheduled to undergo an exam or test that involves contrast agents, or have had one within the past 48 hours, please discuss this with your doctor.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Any natural products or vitamins you are using
* Your complete medical history, including any health problems you are experiencing
This information will help your doctor determine whether it is safe for you to take this medication in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Acidic blood problems
+ Kidney disease
+ Liver disease
Recent medical events, such as a heart attack or stroke
Any difficulties with eating or drinking, including situations where you may be required to fast before a procedure or surgery
Additionally, if you are scheduled to undergo an exam or test that involves contrast agents, or have had one within the past 48 hours, please discuss this with your doctor.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter medications you are taking
Any natural products or vitamins you are using
* Your complete medical history, including any health problems you are experiencing
This information will help your doctor determine whether it is safe for you to take this medication in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Before consuming alcohol, discuss the potential risks with your doctor.
If you experience low blood sugar, do not operate a vehicle, as this can increase your risk of being involved in an accident. Monitor your blood sugar levels as directed by your doctor, and undergo blood tests as scheduled to ensure your condition is being properly managed. Discuss any concerns or questions with your doctor.
During periods of stress, such as fever, infection, injury, or surgery, it may be more challenging to control your blood sugar levels. Changes in physical activity, exercise, or diet can also impact your blood sugar. Adhere to the diet and exercise plan recommended by your doctor to maintain optimal control.
If you experience diarrhea or vomiting, contact your doctor promptly, as you may need to increase your fluid intake to prevent excessive fluid loss. Be cautious in hot weather or during intense physical activity, and drink plenty of fluids to avoid dehydration.
Long-term treatment with metformin may lead to decreased vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult with your doctor. Additionally, if you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
For individuals of childbearing age who have not been ovulating, there is a potential risk of pregnancy. To avoid pregnancy, use birth control while taking this medication. If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor to discuss the benefits and risks of this medication for both you and your baby.
If you experience low blood sugar, do not operate a vehicle, as this can increase your risk of being involved in an accident. Monitor your blood sugar levels as directed by your doctor, and undergo blood tests as scheduled to ensure your condition is being properly managed. Discuss any concerns or questions with your doctor.
During periods of stress, such as fever, infection, injury, or surgery, it may be more challenging to control your blood sugar levels. Changes in physical activity, exercise, or diet can also impact your blood sugar. Adhere to the diet and exercise plan recommended by your doctor to maintain optimal control.
If you experience diarrhea or vomiting, contact your doctor promptly, as you may need to increase your fluid intake to prevent excessive fluid loss. Be cautious in hot weather or during intense physical activity, and drink plenty of fluids to avoid dehydration.
Long-term treatment with metformin may lead to decreased vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult with your doctor. Additionally, if you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
For individuals of childbearing age who have not been ovulating, there is a potential risk of pregnancy. To avoid pregnancy, use birth control while taking this medication. If you are pregnant, plan to become pregnant, or are breastfeeding, inform your doctor to discuss the benefits and risks of this medication for both you and your baby.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (severe metabolic acidosis with elevated lactate levels)
- Severe gastrointestinal upset (nausea, vomiting, diarrhea)
- Hypoglycemia (rare with monotherapy, more likely with concomitant insulin or sulfonylureas)
- Hypotension
- Bradyarrhythmias
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Treatment for lactic acidosis involves supportive measures and prompt hemodialysis to remove metformin and correct acidosis.
Drug Interactions
Contraindicated Interactions
- Iodinated Contrast Media (temporarily discontinue at or prior to procedure, restart 48 hours after if renal function stable)
- Alcohol (excessive acute or chronic use)
Major Interactions
- Carbonic Anhydrase Inhibitors (e.g., topiramate, zonisamide, acetazolamide, dichlorphenamide) - increased risk of lactic acidosis
- Drugs that reduce metformin clearance (e.g., cimetidine, ranolazine, dolutegravir, isavuconazonium, trimethoprim, vandetanib) - increased metformin levels and lactic acidosis risk
- Drugs that affect renal function (e.g., NSAIDs, ACE inhibitors, ARBs, diuretics) - increased risk of lactic acidosis due to potential for acute kidney injury
Moderate Interactions
- Corticosteroids (systemic) - may increase blood glucose, requiring metformin dose adjustment
- Thiazide Diuretics - may increase blood glucose, requiring metformin dose adjustment
- Sympathomimetics - may increase blood glucose
- Phenothiazines - may increase blood glucose
- Thyroid products - may increase blood glucose
- Oral Contraceptives - may increase blood glucose
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To assess baseline kidney function and determine appropriate dosing, as metformin is renally eliminated and contraindicated in severe renal impairment.
Timing: Prior to initiation of therapy
HbA1c
Rationale: To establish baseline glycemic control and guide initial therapy.
Timing: Prior to initiation of therapy
Liver function tests (LFTs)
Rationale: To assess baseline hepatic function, as severe hepatic impairment is a contraindication due to increased lactic acidosis risk.
Timing: Prior to initiation of therapy
Routine Monitoring
Renal function (eGFR)
Frequency: At least annually; more frequently (every 3-6 months) in elderly, those with moderate renal impairment, or those at risk of renal impairment.
Target: >60 mL/min/1.73m² (optimal); >30 mL/min/1.73m² (acceptable with dose adjustment)
Action Threshold: Discontinue if eGFR < 30 mL/min/1.73m²; adjust dose if eGFR 30-59 mL/min/1.73m².
HbA1c
Frequency: Every 3-6 months
Target: <7% (individualized based on patient factors)
Action Threshold: If target not met, consider dose titration or addition of other antidiabetic agents.
Vitamin B12 levels
Frequency: Periodically (e.g., every 1-2 years) for patients on long-term metformin therapy or those with symptoms of B12 deficiency.
Target: Normal range (e.g., 200-900 pg/mL)
Action Threshold: Supplement B12 if levels are low or patient develops symptoms of deficiency (e.g., anemia, neuropathy).
Blood glucose (fasting and postprandial)
Frequency: Daily or as directed by healthcare provider
Target: Fasting: 80-130 mg/dL; Postprandial: <180 mg/dL (individualized)
Action Threshold: Report persistent high or low readings to healthcare provider.
Symptom Monitoring
- Symptoms of lactic acidosis (e.g., malaise, myalgia, respiratory distress, somnolence, abdominal distress, hypothermia, hypotension, bradyarrhythmias)
- Symptoms of vitamin B12 deficiency (e.g., fatigue, weakness, numbness or tingling, memory problems, sore tongue)
- Gastrointestinal side effects (e.g., nausea, vomiting, diarrhea, abdominal discomfort)
Special Patient Groups
Pregnancy
Metformin crosses the placenta. While older classification was Category B, current guidelines (e.g., ACOG, ADA) suggest that metformin may be continued or initiated in pregnancy for gestational diabetes or pre-existing type 2 diabetes if glycemic control cannot be achieved with diet and exercise, or if there are concerns about excessive weight gain with insulin. Benefits versus risks should be carefully weighed.
Trimester-Specific Risks:
First Trimester:
Limited data, but no clear evidence of increased risk of major birth defects.
Second Trimester:
Generally considered safe for continued use if indicated for glycemic control.
Third Trimester:
Generally considered safe for continued use if indicated for glycemic control.
Lactation
Metformin is excreted into breast milk in small amounts. The amount ingested by the infant is generally considered low and unlikely to cause adverse effects. It is generally considered compatible with breastfeeding (Lactation Risk Category L2). Monitor breastfed infants for signs of hypoglycemia or gastrointestinal upset.
Infant Risk:
Low risk
Pediatric Use
Approved for use in children 10 years of age and older with type 2 diabetes. Dosing should be carefully titrated. Renal function should be monitored, especially in younger children.
Geriatric Use
Use with caution in elderly patients due to increased likelihood of decreased renal function. Renal function should be assessed more frequently. The maximum recommended dose may be lower for elderly patients. Increased risk of lactic acidosis.
Clinical Information
Clinical Pearls
- Metformin is the first-line pharmacologic agent for most patients with type 2 diabetes.
- It is weight-neutral or can cause modest weight loss, and does not cause hypoglycemia when used as monotherapy.
- Gastrointestinal side effects (diarrhea, nausea) are common, especially at initiation. Titrating the dose slowly and taking it with food can help mitigate these.
- Patients should be advised to temporarily discontinue metformin before and for 48 hours after receiving iodinated contrast media or undergoing surgical procedures requiring restricted food/fluid intake.
- Long-term use of metformin can be associated with vitamin B12 deficiency; consider periodic monitoring and supplementation if needed.
- Educate patients on the symptoms of lactic acidosis, a rare but serious side effect.
Alternative Therapies
- Sulfonylureas (e.g., glipizide, glyburide, glimepiride)
- DPP-4 Inhibitors (e.g., sitagliptin, saxagliptin, linagliptin)
- SGLT2 Inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin)
- GLP-1 Receptor Agonists (e.g., liraglutide, semaglutide, dulaglutide)
- Thiazolidinediones (TZDs) (e.g., pioglitazone, rosiglitazone)
- Insulin
- Alpha-glucosidase Inhibitors (e.g., acarbose, miglitol)
- Meglitinides (e.g., repaglinide, nateglinide)
Cost & Coverage
Average Cost:
$10 - $30 per 30 tablets (500mg IR generic)
Generic Available:
Yes
Insurance Coverage:
Tier 1 (Preferred Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.