Glucophage 1000mg 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 agent
Pharmacologic Class
Biguanide
Pregnancy Category
Category B
FDA Approved
Dec 1994
DEA Schedule
Not Controlled
Overview
What is this medicine?
Metformin is a medicine used to help control blood sugar levels in people with type 2 diabetes. It works by reducing the amount of sugar your liver makes, decreasing the sugar your body absorbs from food, and making your body more sensitive to insulin. 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 instructed by your doctor or healthcare provider, even if you start to feel better. It's essential to complete the full course of treatment as prescribed.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication, store it at room temperature, away from direct 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 advises you to do otherwise. 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 instructed by your doctor or healthcare provider, even if you start to feel better. It's essential to complete the full course of treatment as prescribed.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication, store it at room temperature, away from direct 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 advises you to do otherwise. 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.
- 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 it 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: 1000 mg orally twice daily or 850 mg orally three times daily.
Dose Range:
500 - 2550 mg
Condition-Specific Dosing:
Type 2 Diabetes Mellitus:
Initial: 500 mg BID or 850 mg QD. Titrate by 500 mg weekly or 850 mg every 2 weeks. Max: 2550 mg/day (IR) or 2500 mg/day (ER).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For children 10-16 years: Initial 500 mg orally twice daily with meals. Titrate by 500 mg weekly. Max: 2000 mg/day.
Adolescent:
For adolescents 17 years and older: Same as adult dosing.
Dose Adjustments
Renal Impairment:
Mild:
eGFR 60-89 mL/min/1.73m2: No dose adjustment, but monitor renal function annually.
Moderate:
eGFR 45-59 mL/min/1.73m2: Not recommended to initiate. If already on therapy, assess benefits/risks, consider dose reduction (e.g., max 1000 mg/day), and monitor renal function every 3-6 months. eGFR 30-44 mL/min/1.73m2: Not recommended to initiate. If already on therapy, discontinue.
Severe:
eGFR < 30 mL/min/1.73m2: Contraindicated.
Dialysis:
Contraindicated in patients on dialysis due to increased risk of lactic acidosis.
Hepatic Impairment:
Mild:
No specific guidelines, 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 decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. It does not stimulate insulin secretion and therefore does not cause hypoglycemia in monotherapy.
Pharmacokinetics
Absorption:
Bioavailability:
50-60%
Tmax:
2-2.5 hours (immediate release)
FoodEffect:
Food decreases the extent and slightly delays the absorption of metformin.
Distribution:
Vd:
654 Âą 358 L
ProteinBinding:
< 5%
CnssPenetration:
Limited
Elimination:
HalfLife:
Plasma elimination half-life is approximately 6.2 hours; blood half-life is approximately 17.6 hours.
Clearance:
Renal clearance is approximately 3.5 times higher than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Renal (unchanged)
Unchanged:
> 90%
Pharmacodynamics
OnsetOfAction:
Days to weeks for full glucose-lowering effect
PeakEffect:
Peak glucose-lowering effect typically seen after several weeks of consistent dosing.
DurationOfAction:
Approximately 12-24 hours (for IR formulation, requiring BID/TID dosing)
Confidence:
Medium
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:
- Symptoms of lactic acidosis: unusual muscle pain, trouble breathing, stomach discomfort, dizziness, lightheadedness, feeling cold, or unusual tiredness/weakness.
- Symptoms of low blood sugar (hypoglycemia) if taken with other diabetes medications: sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet.
- Symptoms of vitamin B12 deficiency: unusual tiredness, weakness, numbness or tingling in hands or feet.
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 normally, which may be relevant before undergoing certain procedures or surgery
* Upcoming or recent exams or tests that involve contrast agents, particularly if they have taken place within the past 48 hours. Discuss these procedures with your doctor to ensure safe management.
This list is not exhaustive, and it is crucial to disclose all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues to your doctor and pharmacist. This will help determine whether it is safe to take this medication in conjunction with your other treatments 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 normally, which may be relevant before undergoing certain procedures or surgery
* Upcoming or recent exams or tests that involve contrast agents, particularly if they have taken place within the past 48 hours. Discuss these procedures with your doctor to ensure safe management.
This list is not exhaustive, and it is crucial to disclose all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues to your doctor and pharmacist. This will help determine whether it is safe to take this medication in conjunction with your other treatments 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, avoid driving, as it increases the risk of accidents. Monitor your blood sugar levels as instructed by your doctor. Additionally, follow your doctor's recommendations for regular blood tests to ensure your overall health.
Be aware that stress, such as fever, infection, injury, or surgery, can affect blood sugar control. Changes in physical activity, exercise, or diet can also impact your blood sugar levels. Adhere to the diet and exercise plan recommended by your doctor to maintain optimal blood sugar control.
If you experience diarrhea or vomiting, contact your doctor promptly, as you may need to increase fluid intake to prevent excessive fluid loss. In hot weather or during physical activity, drink plenty of fluids to avoid dehydration.
Long-term use of metformin may lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult your doctor. Individuals 65 years or older should use this medication with caution, as they may be more susceptible to side effects.
Women of childbearing age who have not been ovulating may be at risk of pregnancy while taking this medication. To avoid pregnancy, use birth control measures while taking this drug. If you are pregnant, plan to become pregnant, or are breastfeeding, discuss the benefits and risks with your doctor to ensure the best possible outcome for you and your baby.
If you experience low blood sugar, avoid driving, as it increases the risk of accidents. Monitor your blood sugar levels as instructed by your doctor. Additionally, follow your doctor's recommendations for regular blood tests to ensure your overall health.
Be aware that stress, such as fever, infection, injury, or surgery, can affect blood sugar control. Changes in physical activity, exercise, or diet can also impact your blood sugar levels. Adhere to the diet and exercise plan recommended by your doctor to maintain optimal blood sugar control.
If you experience diarrhea or vomiting, contact your doctor promptly, as you may need to increase fluid intake to prevent excessive fluid loss. In hot weather or during physical activity, drink plenty of fluids to avoid dehydration.
Long-term use of metformin may lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult your doctor. Individuals 65 years or older should use this medication with caution, as they may be more susceptible to side effects.
Women of childbearing age who have not been ovulating may be at risk of pregnancy while taking this medication. To avoid pregnancy, use birth control measures while taking this drug. If you are pregnant, plan to become pregnant, or are breastfeeding, discuss the benefits and risks with your doctor to ensure the best possible outcome for you and your baby.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (severe metabolic acidosis, hypothermia, hypotension, resistant bradyarrhythmias)
- Hypoglycemia (if co-administered with sulfonylureas or insulin)
- Severe gastrointestinal upset (nausea, vomiting, diarrhea)
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Treatment involves supportive care and prompt hemodialysis to remove metformin and correct acidosis.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast agents (temporarily discontinue metformin at the time of or prior to the procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure; restart metformin if renal function is stable.)
Major Interactions
Moderate Interactions
- Drugs that reduce metformin clearance (e.g., ranolazine, vandetanib, dolutegravir, isavuconazole, cimetidine, trimethoprim, verapamil, rifampicin, crizotinib, olaparib) (may increase metformin levels)
- Diuretics (thiazide and loop) (may increase blood glucose, requiring dose adjustment of metformin)
- Corticosteroids (may increase blood glucose, requiring dose adjustment of metformin)
- Sympathomimetics (may increase blood glucose, requiring dose adjustment of metformin)
- Phenothiazines (may increase blood glucose, requiring dose adjustment of metformin)
- Thyroid products (may increase blood glucose, requiring dose adjustment of metformin)
Minor Interactions
- Nifedipine (enhances absorption and excretion of metformin, minor clinical significance)
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: Metformin is primarily renally excreted; impaired renal function increases risk of lactic acidosis.
Timing: Prior to initiation of therapy.
HbA1c
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Blood glucose
Rationale: To establish baseline glycemic control.
Timing: Prior to initiation of therapy.
Vitamin B12 levels (consider)
Rationale: Long-term metformin use can be associated with vitamin B12 deficiency.
Timing: Prior to initiation, especially in patients with risk factors for B12 deficiency or neuropathy.
Routine Monitoring
HbA1c
Frequency: Every 3-6 months
Target: Individualized, typically < 7.0% for most adults
Action Threshold: If above target, consider dose adjustment or addition of other agents.
Renal function (eGFR)
Frequency: At least annually; more frequently (e.g., every 3-6 months) in patients with eGFR 45-59 mL/min/1.73m2 or elderly patients.
Target: > 30 mL/min/1.73m2
Action Threshold: If eGFR falls below 45 mL/min/1.73m2, reassess therapy; if below 30 mL/min/1.73m2, discontinue.
Blood glucose (fasting and postprandial)
Frequency: Daily self-monitoring or as directed by physician
Target: Fasting: 80-130 mg/dL; Postprandial: < 180 mg/dL
Action Threshold: Persistent readings outside target range may indicate need for dose adjustment or additional therapy.
Vitamin B12 levels
Frequency: Periodically (e.g., every 2-3 years) or if symptoms of deficiency (e.g., anemia, neuropathy) develop.
Target: Normal range (e.g., > 200 pg/mL)
Action Threshold: If low, consider supplementation.
Symptom Monitoring
- Symptoms of lactic acidosis (malaise, myalgia, respiratory distress, somnolence, abdominal distress, hypothermia, hypotension, resistant bradyarrhythmias)
- Symptoms of hypoglycemia (if used in combination with insulin or sulfonylureas) (sweating, tremor, hunger, confusion, dizziness)
- Gastrointestinal side effects (nausea, vomiting, diarrhea, abdominal discomfort)
- Symptoms of vitamin B12 deficiency (fatigue, weakness, numbness, tingling, memory problems)
Special Patient Groups
Pregnancy
Metformin is generally not the first-line treatment for gestational diabetes or type 2 diabetes in pregnancy, with insulin being preferred. However, it may be considered in certain cases where insulin is not feasible or acceptable, or for women with polycystic ovary syndrome (PCOS) who become pregnant. It crosses the placenta.
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 initiated prior to pregnancy or if benefits outweigh risks.
Third Trimester:
Generally considered safe for continued use if initiated prior to pregnancy or if benefits outweigh risks. Monitor for neonatal hypoglycemia.
Lactation
Metformin is excreted into breast milk in small amounts. It is generally considered compatible with breastfeeding, and adverse effects in breastfed infants are unlikely. Monitor breastfed infants for signs of hypoglycemia.
Infant Risk:
Low risk (L2 - Safer)
Pediatric Use
Approved for children 10 years and older for type 2 diabetes. Dosing is weight-based and titrated. Monitor renal function and B12 levels. Gastrointestinal side effects are common.
Geriatric Use
Use with caution due to increased likelihood of decreased renal function in elderly patients, which increases the risk of lactic acidosis. Assess renal function more frequently. Avoid initiation in patients âĨ 80 years of age unless renal function is normal.
Clinical Information
Clinical Pearls
- Metformin is considered first-line pharmacologic therapy for type 2 diabetes mellitus, especially in overweight or obese patients, due to its efficacy, low risk of hypoglycemia (as monotherapy), and potential for modest weight loss.
- Gastrointestinal side effects (nausea, diarrhea, abdominal discomfort) are common, especially at initiation. These can be minimized by starting with a low dose, titrating slowly, and taking the medication with food.
- Extended-release (XR) formulations may improve GI tolerability.
- Patients should be educated on the symptoms of lactic acidosis and instructed to seek immediate medical attention if they occur.
- Temporarily discontinue metformin before or at the time of iodinated contrast imaging procedures and before surgical procedures requiring restricted food/fluid intake or other situations that may lead to hypoperfusion/hypoxemia.
- Long-term use of metformin can be associated with vitamin B12 deficiency; consider periodic monitoring, especially in patients with neuropathy or anemia.
Alternative Therapies
- Sulfonylureas (e.g., glipizide, glyburide, glimepiride)
- Thiazolidinediones (e.g., pioglitazone, rosiglitazone)
- DPP-4 inhibitors (e.g., sitagliptin, saxagliptin, linagliptin, alogliptin)
- SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin, ertugliflozin)
- GLP-1 receptor agonists (e.g., liraglutide, semaglutide, dulaglutide, exenatide)
- Insulin
- Alpha-glucosidase inhibitors (e.g., acarbose, miglitol)
- Meglitinides (e.g., repaglinide, nateglinide)
- Amylin analog (pramlintide)
Cost & Coverage
Average Cost:
Varies widely, typically $10-$30 per 30 tablets (for generic 1000mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 (Preferred Generic) for generic metformin; Tier 2-3 for brand-name formulations.
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 seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to ensure you receive the best possible care.