Glumetza 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 agent
Pharmacologic Class
Biguanide
Pregnancy Category
Not available
FDA Approved
Jun 2005
DEA Schedule
Not Controlled
Overview
What is this medicine?
Glumetza is an extended-release tablet containing metformin, a medicine used to help control high 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 usually taken once a day with your evening meal.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with meals as directed. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you feel well. If you are taking this medication once daily, take it with your evening meal. Swallow the medication whole; do not chew, break, or crush it. If you have difficulty swallowing, consult your doctor.
Storing and Disposing of Your Medication
Store your medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom. Keep all medications in a safe location, out of the reach of children and pets.
Missing 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 use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with meals as directed. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you feel well. If you are taking this medication once daily, take it with your evening meal. Swallow the medication whole; do not chew, break, or crush it. If you have difficulty swallowing, consult your doctor.
Storing and Disposing of Your Medication
Store your medication at room temperature, protected from light, and in a dry place. Avoid storing it in a bathroom. Keep all medications in a safe location, out of the reach of children and pets.
Missing 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.
Lifestyle & Tips
- Follow a balanced diet as recommended by your doctor or dietitian.
- Engage in regular physical activity as advised by your healthcare provider.
- Monitor your blood sugar levels regularly as instructed.
- Limit alcohol intake, as excessive alcohol can increase the risk of a serious side effect called lactic acidosis.
- Stay well-hydrated, especially during illness or strenuous exercise.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 500 mg orally once daily with the evening meal. Titrate by 500 mg weekly to a maximum of 2000 mg once daily.
Dose Range:
500 - 2000 mg
Condition-Specific Dosing:
Type 2 Diabetes Mellitus:
Initial: 500 mg orally once daily with the evening meal. Increase dosage in increments of 500 mg weekly, up to a maximum of 2000 mg once daily. If glycemic control is not achieved at 2000 mg once daily, consider 1000 mg twice daily. Glumetza 500mg and 1000mg tablets are available.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (Metformin immediate-release is approved for children âĨ10 years; extended-release forms like Glumetza are generally not recommended for pediatric use due to lack of specific studies and different pharmacokinetic profiles compared to IR)
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 500 mg once daily. Maximum dose 1000 mg once daily. 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% and monitor eGFR every 3 months.
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:
Use with caution. Monitor liver function.
Moderate:
Use with caution. Increased risk of lactic acidosis. Consider lower doses and close monitoring.
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, 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 in monotherapy.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 50-60% (for immediate-release; extended-release formulations have different absorption profiles designed for slower release)
Tmax:
Glumetza: Approximately 7 hours (range 4-12 hours) after a single dose with food.
FoodEffect:
Food increases the absorption of Glumetza, increasing AUC by approximately 35% and Cmax by 40% compared to fasting conditions. Should be taken with the evening meal.
Distribution:
Vd:
654 Âą 358 L (for immediate-release)
ProteinBinding:
< 5%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 6.2 hours (plasma); 17.6 hours (blood) for immediate-release. For Glumetza, the effective half-life is longer due to extended absorption.
Clearance:
Renal clearance is approximately 3.5 times higher than creatinine clearance, indicating tubular secretion.
ExcretionRoute:
Renal (primarily unchanged in urine)
Unchanged:
> 90%
Pharmacodynamics
OnsetOfAction:
Gradual, typically within days to weeks for full glycemic effect.
PeakEffect:
Glycemic effects are typically seen within 1-2 weeks, with maximal effects often taking 4-6 weeks.
DurationOfAction:
24 hours (due to extended-release formulation)
Confidence:
High
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 Glumetza and institute general supportive measures promptly 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 signs or 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, which may be more likely when this medication is used with other diabetes drugs. Symptoms 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 signs or 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, which may be more likely when this medication is used with other diabetes drugs. Symptoms 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, unusual sleepiness, stomach pain, nausea, vomiting, feeling cold, dizziness, or a slow or irregular heartbeat. Seek immediate medical attention.
- Symptoms of low blood sugar (hypoglycemia) if taken with other diabetes medications: sweating, shaking, fast heartbeat, hunger, confusion, dizziness, or tingling in hands/feet.
- Symptoms of vitamin B12 deficiency: unusual tiredness, weakness, numbness or tingling in hands/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, including situations where you may be required to fast before a procedure or surgery
* Upcoming or recent exams or tests that involve contrast agents, particularly if they have taken place within the past 48 hours
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if 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, including situations where you may be required to fast before a procedure or surgery
* Upcoming or recent exams or tests that involve contrast agents, particularly if they have taken place within the past 48 hours
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if 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 directed by your doctor. Regular blood tests, as scheduled by your doctor, are also crucial to ensure the medication's effectiveness and your overall health. Discuss any concerns or questions with your doctor.
During stressful periods, such as illness, infection, injury, or surgery, your blood sugar levels may be more challenging to 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 dehydration. In hot weather or during intense physical activity, drink plenty of fluids to avoid fluid loss.
Long-term use of metformin may lead to decreased vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult your doctor. You may notice the appearance of the tablet in your stool; however, this is a normal occurrence and not a cause for concern. If you have any questions, discuss them with your doctor.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects. Women of childbearing age who have not been ovulating may experience a renewed 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. It is crucial to discuss the potential benefits and risks of this medication to both 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 directed by your doctor. Regular blood tests, as scheduled by your doctor, are also crucial to ensure the medication's effectiveness and your overall health. Discuss any concerns or questions with your doctor.
During stressful periods, such as illness, infection, injury, or surgery, your blood sugar levels may be more challenging to 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 dehydration. In hot weather or during intense physical activity, drink plenty of fluids to avoid fluid loss.
Long-term use of metformin may lead to decreased vitamin B-12 levels. If you have a history of low vitamin B-12 levels, consult your doctor. You may notice the appearance of the tablet in your stool; however, this is a normal occurrence and not a cause for concern. If you have any questions, discuss them with your doctor.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects. Women of childbearing age who have not been ovulating may experience a renewed 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. It is crucial to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Lactic acidosis (most serious and common symptom)
- Hypoglycemia (less common with metformin monotherapy, but possible with co-ingestion of other agents or in severe overdose)
- Gastrointestinal upset (nausea, vomiting, diarrhea)
What to Do:
Call 1-800-222-1222 (Poison Control). Immediate medical attention is required. Treatment for lactic acidosis involves supportive measures and prompt hemodialysis to remove metformin and correct acidosis.
Drug Interactions
Contraindicated Interactions
Major Interactions
- Cimetidine (increases metformin plasma concentration)
- Ranolazine (increases metformin plasma concentration)
- Dolutegravir (increases metformin plasma concentration)
- Dofetilide (may increase dofetilide levels)
- Carbonic anhydrase inhibitors (e.g., topiramate, zonisamide, acetazolamide, dichlorphenamide - may increase risk of lactic acidosis)
Moderate Interactions
- Nifedipine (increases metformin absorption and excretion)
- Furosemide (increases metformin plasma concentration and Cmax)
- Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, trimethoprim, vancomycin - compete for renal tubular secretion, potentially increasing metformin levels)
- Drugs that affect glycemic control (e.g., corticosteroids, diuretics, thyroid products, oral contraceptives, phenothiazines, sympathomimetics, calcium channel blockers, isoniazid, niacin, sulfonylureas, insulin - may require dose adjustment of metformin or concomitant agent)
- NSAIDs, ACE inhibitors, ARBs (may worsen renal function, increasing lactic acidosis risk)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To assess baseline kidney function and determine appropriate dosing, as metformin is primarily renally eliminated and accumulation can lead to lactic acidosis.
Timing: Prior to initiation of therapy.
HbA1c
Rationale: To establish baseline glycemic control and guide initial therapy.
Timing: Prior to initiation of therapy.
Vitamin B12 levels
Rationale: Metformin can decrease vitamin B12 absorption.
Timing: Consider baseline, especially in patients at risk for deficiency.
Routine Monitoring
HbA1c
Frequency: Every 3-6 months
Target: Individualized, typically < 7% for most adults (ADA guidelines)
Action Threshold: If target not met, consider dose adjustment or addition of other agents.
Renal function (eGFR)
Frequency: At least annually; more frequently (every 3-6 months) in patients with eGFR 30-59 mL/min/1.73m2, elderly, or those at risk for renal impairment.
Target: > 60 mL/min/1.73m2 for full dose; > 30 mL/min/1.73m2 for continued use with dose adjustment.
Action Threshold: Discontinue if eGFR falls below 30 mL/min/1.73m2. Reassess if eGFR falls below 45 mL/min/1.73m2.
Vitamin B12 levels
Frequency: Periodically, especially if anemia or neuropathy symptoms develop.
Target: Normal range (e.g., > 200 pg/mL)
Action Threshold: Supplement if levels are low or symptoms of deficiency are present.
Blood glucose (fasting and postprandial)
Frequency: Daily or as directed by healthcare provider
Target: Individualized (e.g., FBG 80-130 mg/dL, PPG < 180 mg/dL)
Action Threshold: Adjust diet, exercise, or medication based on readings.
Symptom Monitoring
- Symptoms of lactic acidosis (malaise, myalgia, respiratory distress, somnolence, abdominal distress, hypothermia, hypotension, bradyarrhythmias)
- Symptoms of hypoglycemia (if used with insulin or sulfonylureas)
- Symptoms of vitamin B12 deficiency (fatigue, weakness, peripheral neuropathy, megaloblastic anemia)
- Gastrointestinal side effects (diarrhea, nausea, vomiting, abdominal discomfort)
Special Patient Groups
Pregnancy
Metformin is generally considered a reasonable option for managing gestational diabetes or type 2 diabetes in pregnancy, especially when insulin is not preferred or sufficient. However, insulin is often the preferred first-line agent for glycemic control in pregnancy. The benefits and risks should be carefully weighed.
Trimester-Specific Risks:
First Trimester:
Limited data, but no clear evidence of increased risk of congenital malformations.
Second Trimester:
Generally considered safe and effective for glycemic control.
Third Trimester:
Generally considered safe and effective for glycemic control.
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 infant for signs of hypoglycemia or gastrointestinal upset.
Infant Risk:
Low risk (L2)
Pediatric Use
Glumetza (metformin extended-release) is not approved for pediatric use. Metformin immediate-release is approved for children 10 years and older for type 2 diabetes. Safety and efficacy of Glumetza in pediatric patients have not been established.
Geriatric Use
Use with caution in elderly patients due to increased likelihood of decreased renal function, which increases the risk of lactic acidosis. Renal function should be assessed more frequently. Start with lower doses and titrate slowly.
Clinical Information
Clinical Pearls
- Glumetza should be taken with the evening meal to optimize absorption and minimize GI side effects.
- Extended-release formulations like Glumetza may have fewer gastrointestinal side effects (e.g., diarrhea) compared to immediate-release metformin.
- Patients should be educated on the symptoms of lactic acidosis and instructed to seek immediate medical attention if they occur.
- Temporarily discontinue Glumetza before or at the time of iodinated contrast imaging procedures and before any surgical procedures requiring restricted food/fluid intake.
- Regular monitoring of renal function is crucial, especially in elderly patients or those with comorbidities.
- Consider periodic vitamin B12 level checks, especially in patients on long-term metformin therapy or those with risk factors for B12 deficiency.
Alternative Therapies
- Other oral antidiabetic agents (e.g., sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, thiazolidinediones, meglitinides, alpha-glucosidase inhibitors)
- Insulin therapy
- Lifestyle modifications (diet and exercise)
Cost & Coverage
Average Cost:
$100 - $300 per 30 tablets (Glumetza 500mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (for generic metformin ER); Tier 3 or higher (for brand Glumetza)
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 your 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 emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.