Xigduo XR 10mg/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 help control blood sugar in people with type 2 diabetes.It is used in certain people to lower the risk of death and having to go to the hospital because of heart failure.It is used in people with certain kidney problems to lower the risk of worsening kidney problems.
Drug Class
Antidiabetic agent, combination
Pharmacologic Class
Sodium-glucose cotransporter 2 (SGLT2) inhibitor and Biguanide
Pregnancy Category
Not available
FDA Approved
Oct 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
Xigduo XR is a combination medicine used to help control high blood sugar in adults with type 2 diabetes. It contains two active ingredients: dapagliflozin and metformin extended-release. Dapagliflozin works by helping your kidneys remove more sugar from your body through your urine. Metformin works by reducing the amount of sugar your liver makes and helping your body use insulin more effectively. This medicine is used along with diet and exercise.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
Take your medication with food, preferably in the morning.
Swallow the tablet whole - do not chew, break, or crush it.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To ensure your medication remains effective and safe:
Store it at room temperature in a dry place, away from the bathroom.
Keep all medications in a secure location, out of reach of children and pets.
Dispose of unused or expired medication properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your doctor or pharmacist.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also have access to local drug take-back programs.
What to Do If You Miss a Dose
If you miss a dose of your medication:
Take it as soon as you remember.
If it's close to the time for your next dose, skip the missed dose and resume your regular schedule.
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, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
Take your medication with food, preferably in the morning.
Swallow the tablet whole - do not chew, break, or crush it.
Drink plenty of non-caffeinated liquids, unless your doctor advises you to limit your fluid intake.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To ensure your medication remains effective and safe:
Store it at room temperature in a dry place, away from the bathroom.
Keep all medications in a secure location, out of reach of children and pets.
Dispose of unused or expired medication properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your doctor or pharmacist.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also have access to local drug take-back programs.
What to Do If You Miss a Dose
If you miss a dose of your medication:
Take it as soon as you remember.
If it's close to the time for your next dose, skip the missed dose and resume your regular schedule.
Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Follow a healthy diet plan as recommended by your doctor or dietitian.
- Engage in regular physical activity as advised by your healthcare provider.
- Stay well-hydrated, especially when exercising or in hot weather, to reduce the risk of dehydration.
- Limit or avoid alcohol consumption, as it can increase the risk of lactic acidosis with metformin.
- Monitor your blood sugar levels regularly as instructed by your doctor.
- Maintain good personal hygiene, especially genital and urinary tract hygiene, to reduce the risk of infections.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: Dapagliflozin 5 mg/Metformin XR 500 mg orally once daily in the morning with food. Titrate based on efficacy and tolerability. Maintenance: Dapagliflozin 10 mg/Metformin XR 1000 mg to 2000 mg orally once daily.
Dose Range:
500 - 2000 mg
Condition-Specific Dosing:
initialTherapy:
Dapagliflozin 5 mg/Metformin XR 500 mg once daily.
patientsOnMetformin:
Switch to Xigduo XR containing dapagliflozin 5 mg or 10 mg and metformin XR equivalent to the current metformin dose.
patientsOnDapagliflozin:
Switch to Xigduo XR containing dapagliflozin 5 mg or 10 mg and metformin XR 500 mg, titrating metformin XR dose gradually.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
eGFR 45 to <60 mL/min/1.73m²: Initiate with or continue dapagliflozin 5 mg once daily. Metformin dose may need adjustment based on eGFR.
Moderate:
eGFR 30 to <45 mL/min/1.73m²: Not recommended to initiate. If already on, discontinue dapagliflozin. Metformin dose should not exceed 1000 mg/day.
Severe:
eGFR <30 mL/min/1.73m²: Contraindicated.
Dialysis:
Contraindicated.
Hepatic Impairment:
Mild:
No dose adjustment for dapagliflozin. Metformin: Use with caution, monitor for lactic acidosis.
Moderate:
No dose adjustment for dapagliflozin. Metformin: Use with caution, monitor for lactic acidosis.
Severe:
Not recommended for use due to increased risk of lactic acidosis with metformin.
Pharmacology
Mechanism of Action
Dapagliflozin is a highly potent and selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) in the kidneys. By inhibiting SGLT2, it reduces glucose reabsorption from the glomerular filtrate, leading to increased urinary glucose excretion (glucosuria) and a reduction in blood glucose levels. Metformin is a biguanide that acts primarily by decreasing hepatic glucose production (gluconeogenesis and glycogenolysis), 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:
Dapagliflozin: ~78%; Metformin: 50-60% (oral)
Tmax:
Dapagliflozin: 0.5-2 hours; Metformin: 4-8 hours (XR)
FoodEffect:
Dapagliflozin: No clinically meaningful effect; Metformin: Food decreases Cmax and AUC slightly but extends Tmax.
Distribution:
Vd:
Dapagliflozin: 118 L; Metformin: 654 L
ProteinBinding:
Dapagliflozin: ~91%; Metformin: Negligible
CnssPenetration:
Limited
Elimination:
HalfLife:
Dapagliflozin: ~12.9 hours; Metformin: ~6.2 hours (plasma), ~17.6 hours (blood)
Clearance:
Dapagliflozin: 207 mL/min; Metformin: Renal clearance is ~3.5 times greater than creatinine clearance
ExcretionRoute:
Dapagliflozin: Urine (75%), Feces (21%); Metformin: Urine (primarily unchanged)
Unchanged:
Dapagliflozin: <1% (urine); Metformin: ~90% (urine)
Pharmacodynamics
OnsetOfAction:
Dapagliflozin: Within 30 minutes (glucosuria); Metformin: Within hours (glucose lowering)
PeakEffect:
Dapagliflozin: 1-2 hours; Metformin: 4-8 hours (XR)
DurationOfAction:
Dapagliflozin: 24 hours; Metformin: 24 hours (XR)
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 pain. 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 Xigduo XR 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 symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of fluid and electrolyte problems: mood changes, confusion, muscle pain or weakness, irregular or rapid heartbeat, severe dizziness or fainting, increased thirst, seizures, extreme fatigue or weakness, decreased appetite, inability to urinate or changes in urine output, dry mouth, dry eyes, or severe nausea and vomiting.
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Signs of a urinary tract infection (UTI): blood in the urine, painful or burning urination, frequent or urgent need to urinate, fever, lower abdominal pain, or pelvic pain.
Vaginal yeast infection: report itching, unusual odor, or discharge.
Yeast infection of the penis: report pain, swelling, rash, or discharge.
Severe stomach pain.
Stomach problems that occur later during treatment, such as upset stomach, vomiting, or diarrhea, which may be a sign of lactic acidosis (a condition where the blood becomes too acidic).
Rare but Serious Infections
A rare but potentially life-threatening infection can occur with medications like this one. Seek medical help immediately if you experience:
Tender, red, or swollen genitals or the area between your genitals and rectum, accompanied by fever or feeling unwell.
Low Blood Sugar
Low blood sugar can occur, especially when this medication is used with other diabetes medications. Signs of low blood sugar may include:
Dizziness, headache, feeling sleepy or weak, shaking, rapid heartbeat, confusion, hunger, or sweating.
If you experience any of these symptoms, contact your doctor right away and follow their instructions for managing low blood sugar, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other 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 report any concerns to your doctor. Common side effects include:
Diarrhea, upset stomach, or vomiting.
Headache.
Nose or throat irritation.
If you experience any of these side effects or any other symptoms that bother you or do not go away, contact your doctor for advice. 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 immediately or seek emergency medical attention:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of fluid and electrolyte problems: mood changes, confusion, muscle pain or weakness, irregular or rapid heartbeat, severe dizziness or fainting, increased thirst, seizures, extreme fatigue or weakness, decreased appetite, inability to urinate or changes in urine output, dry mouth, dry eyes, or severe nausea and vomiting.
Signs of kidney problems: inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Signs of a urinary tract infection (UTI): blood in the urine, painful or burning urination, frequent or urgent need to urinate, fever, lower abdominal pain, or pelvic pain.
Vaginal yeast infection: report itching, unusual odor, or discharge.
Yeast infection of the penis: report pain, swelling, rash, or discharge.
Severe stomach pain.
Stomach problems that occur later during treatment, such as upset stomach, vomiting, or diarrhea, which may be a sign of lactic acidosis (a condition where the blood becomes too acidic).
Rare but Serious Infections
A rare but potentially life-threatening infection can occur with medications like this one. Seek medical help immediately if you experience:
Tender, red, or swollen genitals or the area between your genitals and rectum, accompanied by fever or feeling unwell.
Low Blood Sugar
Low blood sugar can occur, especially when this medication is used with other diabetes medications. Signs of low blood sugar may include:
Dizziness, headache, feeling sleepy or weak, shaking, rapid heartbeat, confusion, hunger, or sweating.
If you experience any of these symptoms, contact your doctor right away and follow their instructions for managing low blood sugar, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other 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 report any concerns to your doctor. Common side effects include:
Diarrhea, upset stomach, or vomiting.
Headache.
Nose or throat irritation.
If you experience any of these side effects or any other symptoms that bother you or do not go away, contact your doctor for advice. 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:
- Signs of dehydration: severe thirst, dry mouth, dizziness, lightheadedness, decreased urination.
- Signs of urinary tract infection (UTI): burning sensation when urinating, frequent urination, urgent need to urinate, pain in the lower abdomen or back, fever.
- Signs of genital yeast infection: itching or irritation in the genital area, rash, unusual discharge.
- Signs of lactic acidosis (rare but serious): unusual muscle pain, unusual sleepiness, stomach pain, nausea, vomiting, trouble breathing, feeling cold, dizziness, slow or irregular heartbeat. Seek immediate medical attention if these occur.
- Signs of low blood sugar (hypoglycemia): sweating, shaking, fast heartbeat, hunger, confusion, dizziness, blurred vision. If these occur, consume a quick source of sugar (e.g., fruit juice, glucose tablets).
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is crucial to inform your doctor about the following conditions and situations to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, and describe the symptoms you experienced.
If you have type 1 diabetes, as this medication is not intended for its treatment.
If you have a condition that affects the acidity of your blood.
If you have kidney disease or are undergoing dialysis.
If you have liver disease.
If you have recently had a heart attack or stroke.
If you are experiencing difficulties with eating or drinking, including situations before certain procedures or surgery.
If you are scheduled for or have had an exam or test that uses contrast media within the past 48 hours, consult with your doctor.
If you are taking or have recently taken immunosuppressive drugs for kidney disease.
If you are pregnant or think you might be pregnant. Do not take this medication during the second or third trimester of pregnancy.
* If you are breastfeeding. It is recommended not to breastfeed while taking this medication.
This list is not exhaustive, and it is essential to discuss all your medications (including 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 with your other treatments and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is crucial to inform your doctor about the following conditions and situations to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, and describe the symptoms you experienced.
If you have type 1 diabetes, as this medication is not intended for its treatment.
If you have a condition that affects the acidity of your blood.
If you have kidney disease or are undergoing dialysis.
If you have liver disease.
If you have recently had a heart attack or stroke.
If you are experiencing difficulties with eating or drinking, including situations before certain procedures or surgery.
If you are scheduled for or have had an exam or test that uses contrast media within the past 48 hours, consult with your doctor.
If you are taking or have recently taken immunosuppressive drugs for kidney disease.
If you are pregnant or think you might be pregnant. Do not take this medication during the second or third trimester of pregnancy.
* If you are breastfeeding. It is recommended not to breastfeed while taking this medication.
This list is not exhaustive, and it is essential to discuss all your medications (including 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 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. Your doctor may advise you to stop taking this drug before certain surgical procedures, and if so, will instruct you on when to resume taking it after the surgery or procedure.
To ensure your safety, avoid driving if you have experienced low blood sugar, as this can increase your risk of being involved in an accident. To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying position, and exercise caution when climbing stairs.
Regular blood work and laboratory tests are crucial, as directed by your doctor. Be aware that this medication may affect the results of certain lab tests, so it is vital to inform all your healthcare providers and laboratory personnel that you are taking this drug. Consult with your doctor to determine the most suitable glucose tests for you to use.
Monitor your blood sugar levels as instructed by your doctor, and discuss any plans to consume alcohol with your doctor beforehand. Adhere to the diet and exercise plan recommended by your doctor, and if you are on a low-salt or salt-free diet, consult with your doctor to ensure safe management.
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 blood sugar levels. In hot weather or during physical activity, drink plenty of fluids to prevent dehydration.
Long-term treatment with metformin may lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, discuss this with your doctor. Additionally, be aware that this medication can increase the risk of ketoacidosis, a condition characterized by excessive acid in the blood or urine, which can be life-threatening. This risk is higher in individuals with diabetes, pancreas problems, or those who are sick, dehydrated, or have undergone surgery. The risk is also increased in people who use insulin and take less than their normal dose or miss a dose. As instructed by your doctor, check your ketone levels regularly, and seek medical attention if you have any questions or concerns.
Severe urinary tract infections (UTIs) have been associated with this medication, and in some cases, hospitalization may be necessary. Kidney problems can also occur, which may require hospitalization or dialysis. If you are unable to drink fluids or experience persistent stomach upset, vomiting, or diarrhea, it is crucial to avoid dehydration. Contact your doctor for guidance on managing these symptoms, as dehydration can lead to low blood pressure or worsen kidney problems.
You may notice the appearance of the tablet in your stool, but this is a normal occurrence and not a cause for concern. If you have any questions, consult with your doctor.
If you are 65 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 return of fertility while taking this medication. To avoid pregnancy, use birth control while taking this drug. If you become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately, as this medication can harm the unborn baby.
To ensure your safety, avoid driving if you have experienced low blood sugar, as this can increase your risk of being involved in an accident. To minimize the risk of dizziness or fainting, rise slowly from a sitting or lying position, and exercise caution when climbing stairs.
Regular blood work and laboratory tests are crucial, as directed by your doctor. Be aware that this medication may affect the results of certain lab tests, so it is vital to inform all your healthcare providers and laboratory personnel that you are taking this drug. Consult with your doctor to determine the most suitable glucose tests for you to use.
Monitor your blood sugar levels as instructed by your doctor, and discuss any plans to consume alcohol with your doctor beforehand. Adhere to the diet and exercise plan recommended by your doctor, and if you are on a low-salt or salt-free diet, consult with your doctor to ensure safe management.
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 blood sugar levels. In hot weather or during physical activity, drink plenty of fluids to prevent dehydration.
Long-term treatment with metformin may lead to low vitamin B-12 levels. If you have a history of low vitamin B-12 levels, discuss this with your doctor. Additionally, be aware that this medication can increase the risk of ketoacidosis, a condition characterized by excessive acid in the blood or urine, which can be life-threatening. This risk is higher in individuals with diabetes, pancreas problems, or those who are sick, dehydrated, or have undergone surgery. The risk is also increased in people who use insulin and take less than their normal dose or miss a dose. As instructed by your doctor, check your ketone levels regularly, and seek medical attention if you have any questions or concerns.
Severe urinary tract infections (UTIs) have been associated with this medication, and in some cases, hospitalization may be necessary. Kidney problems can also occur, which may require hospitalization or dialysis. If you are unable to drink fluids or experience persistent stomach upset, vomiting, or diarrhea, it is crucial to avoid dehydration. Contact your doctor for guidance on managing these symptoms, as dehydration can lead to low blood pressure or worsen kidney problems.
You may notice the appearance of the tablet in your stool, but this is a normal occurrence and not a cause for concern. If you have any questions, consult with your doctor.
If you are 65 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 return of fertility while taking this medication. To avoid pregnancy, use birth control while taking this drug. If you become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately, as this medication can harm the unborn baby.
Overdose Information
Overdose Symptoms:
- Severe hypoglycemia (if taken with insulin/sulfonylurea)
- Lactic acidosis (severe abdominal pain, muscle pain, rapid breathing, weakness, drowsiness)
- Dehydration
- Hypotension
What to Do:
Call 1-800-222-1222 or seek immediate medical attention. Treatment is supportive. Hemodialysis can remove metformin and dapagliflozin.
Drug Interactions
Contraindicated Interactions
- Iodinated contrast media (for metformin, temporarily discontinue)
- Severe renal impairment (eGFR <30 mL/min/1.73m²)
Major Interactions
- Diuretics (loop or thiazide): Increased risk of dehydration and hypotension, especially with dapagliflozin.
- Insulin and insulin secretagogues (sulfonylureas): Increased risk of hypoglycemia.
- Carbonic anhydrase inhibitors (e.g., topiramate, zonisamide, acetazolamide): May increase risk of lactic acidosis with metformin.
- Drugs that reduce metformin clearance (e.g., ranolazine, cimetidine, dolutegravir, isavuconazole, trimethoprim, vandetanib): May increase metformin accumulation and risk of lactic acidosis.
Moderate Interactions
- Alcohol: Potentiates metformin's effect on lactate metabolism, increasing risk of lactic acidosis.
- Corticosteroids, sympathomimetics, diuretics (other than loop/thiazide), thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, calcium channel blockers, isoniazid: May cause hyperglycemia, requiring dose adjustment of Xigduo XR.
- NSAIDs: May impair renal function, increasing metformin accumulation.
Minor Interactions
- Not specifically identified as minor for this combination, but general caution with drugs affecting glucose levels.
Monitoring
Baseline Monitoring
Renal function (eGFR)
Rationale: To assess eligibility and guide dosing, as both components are renally cleared and metformin is contraindicated in severe renal impairment.
Timing: Prior to initiation
HbA1c
Rationale: To establish baseline glycemic control and guide treatment goals.
Timing: Prior to initiation
Electrolytes (especially bicarbonate)
Rationale: To assess for baseline acidosis risk, particularly with metformin.
Timing: Prior to initiation
Vitamin B12 levels
Rationale: Metformin can decrease B12 absorption.
Timing: Prior to initiation, especially in patients at risk for deficiency
Routine Monitoring
HbA1c
Frequency: Every 3-6 months
Target: <7% (individualized)
Action Threshold: >7% (consider dose adjustment or additional therapy)
Renal function (eGFR)
Frequency: At least annually; more frequently in elderly, renally impaired, or during concomitant use of drugs affecting renal function (e.g., diuretics, NSAIDs)
Target: >60 mL/min/1.73m² (optimal)
Action Threshold: <45 mL/min/1.73m² (re-evaluate dapagliflozin, reduce metformin), <30 mL/min/1.73m² (discontinue)
Blood glucose (fasting and postprandial)
Frequency: Daily (patient self-monitoring) or as clinically indicated
Target: Individualized (e.g., FBG 80-130 mg/dL, PPG <180 mg/dL)
Action Threshold: Persistent hyperglycemia or hypoglycemia
Signs/symptoms of dehydration/hypotension
Frequency: Regularly, especially during initiation or with diuretic use
Target: Not applicable
Action Threshold: Symptomatic hypotension, dizziness, orthostasis (consider fluid intake, dose adjustment)
Signs/symptoms of lactic acidosis
Frequency: Regularly, especially in patients with risk factors
Target: Not applicable
Action Threshold: Malaise, myalgia, somnolence, abdominal pain, respiratory distress (seek immediate medical attention)
Vitamin B12 levels
Frequency: Every 2-3 years or if megaloblastic anemia/neuropathy suspected
Target: Normal range
Action Threshold: Low levels (consider supplementation)
Symptom Monitoring
- Increased thirst
- Frequent urination
- Dizziness or lightheadedness (especially upon standing)
- Weakness or fatigue
- Genital itching or discharge (yeast infection symptoms)
- Painful or frequent urination (UTI symptoms)
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Unusual muscle pain (myalgia)
- Difficulty breathing
- Unusual sleepiness or drowsiness (somnolence)
Special Patient Groups
Pregnancy
Not recommended during the second and third trimesters of pregnancy due to potential adverse effects on renal development in the fetus (dapagliflozin). Limited data on metformin use in pregnancy, but generally considered safer than other oral agents if needed. Insulin is generally preferred for glycemic control in pregnancy.
Trimester-Specific Risks:
First Trimester:
Dapagliflozin: Limited human data, animal studies show no adverse effects. Metformin: Limited human data, generally considered low risk.
Second Trimester:
Dapagliflozin: Not recommended due to potential for adverse renal effects in the fetus (based on animal data). Metformin: Generally considered low risk.
Third Trimester:
Dapagliflozin: Not recommended due to potential for adverse renal effects in the fetus (based on animal data). Metformin: Generally considered low risk.
Lactation
Not recommended during breastfeeding. Dapagliflozin is present in animal milk and may pose a risk to the infant. Metformin is excreted into human milk in small amounts, but the clinical significance is unknown. Weigh benefits of breastfeeding against potential risks to the infant.
Infant Risk:
Dapagliflozin: Potential for renal effects and growth inhibition (based on animal data). Metformin: Low risk, but monitor infant for hypoglycemia or GI upset.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients under 18 years of age.
Geriatric Use
Use with caution in elderly patients (≥65 years) due to increased risk of renal impairment, dehydration, and lactic acidosis. Assess renal function more frequently. Start with lower doses and titrate slowly.
Clinical Information
Clinical Pearls
- Instruct patients to take Xigduo XR once daily in the morning with food to reduce gastrointestinal side effects of metformin and ensure proper absorption.
- Emphasize the importance of adequate hydration to minimize the risk of dehydration, hypotension, and acute kidney injury, especially during illness, hot weather, or strenuous exercise.
- Educate patients on the signs and symptoms of genital mycotic infections and urinary tract infections, and advise them to seek medical attention if these occur.
- Stress the critical importance of recognizing symptoms of lactic acidosis (e.g., unusual muscle pain, somnolence, abdominal pain) and seeking immediate medical attention, especially in patients with risk factors.
- Temporarily discontinue Xigduo XR before any iodinated contrast imaging procedures, surgery, or other procedures requiring restricted food/fluid intake, and restart only after renal function is stable.
- Monitor Vitamin B12 levels periodically in patients on long-term metformin therapy, especially if neuropathy or anemia develops.
Alternative Therapies
- Other SGLT2 inhibitors (e.g., Farxiga, Jardiance, Invokana)
- Other biguanides (Metformin monotherapy)
- DPP-4 inhibitors (e.g., Januvia, Tradjenta)
- GLP-1 receptor agonists (e.g., Ozempic, Trulicity)
- Sulfonylureas (e.g., Glipizide, Glyburide)
- Thiazolidinediones (e.g., Pioglitazone)
- Insulin
Cost & Coverage
Average Cost:
$500 - $700 per 30 tablets
Insurance Coverage:
Tier 2 or 3 (preferred or non-preferred brand)
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.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about your medication, don't hesitate to discuss them with your doctor, 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 detailed information about the overdose, including the name of the medication taken, the amount consumed, and the time it occurred.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about your medication, don't hesitate to discuss them with your doctor, 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 detailed information about the overdose, including the name of the medication taken, the amount consumed, and the time it occurred.