Synjardy (Empagliflozin and Metformin) - Oral

Warning:

Synjardy (empagliflozin and metformin) has a boxed warning (a safety warning included on the drug's product label) to warn about the risk of metformin-associated lactic acidosis. Cases of lactic acidosis resulting from metformin use have reportedly led to severe adverse events, such as hypotension (high blood pressure), hypothermia, and death. People at higher risk include those with kidney or liver impairment, those taking certain other medications, and those 65 and older. Contact your healthcare provider and stop taking Synjardy immediately if lactic acidosis is suspected.

What Is Synjardy?

Synjardy is a combination drug with empagliflozin (a sodium-glucose cotransporter 2 inhibitor) and metformin (a biguanide) used to improve blood sugar control in adults with type 2 diabetes. It can also reduce the risk of death from heart disease in some people.

Empagliflozin stops the kidneys from reabsorbing blood sugar. It also helps your body get rid of excess glucose through urination. Therefore, it lowers glucose levels in people with diabetes. Empagliflozin also has an added benefit for people with heart failure. It protects the heart and lessens the risk of cardiovascular death.

Metformin controls blood sugar levels by decreasing the amount of sugar absorbed from food and the amount of sugar made in the liver. It also helps the body respond better to a hormone called insulin. Insulin helps move the sugar from your blood into your muscles, where it is used for energy. If your insulin isn't working well, more sugar stays in the blood, damaging blood vessels. Metformin also lowers low-density lipoprotein cholesterol, weight, plaque buildup, and the risk of dying from heart disease.

Synjardy is a prescription drug available as extended-release (Synjardy XR) and immediate-release (IR) tablets.

Drug Facts

Generic Name: Empagliflozin and metformin

Brand Name(s): Synjardy, Synjardy XR

Drug Availability: Prescription

Administration Route: Oral

Therapeutic Classification: Hypoglycemic

Available Generically: No

Controlled Substance: N/A

Active Ingredient: Empagliflozin and metformin

Dosage Form(s): Tablet, extended-release tablet

What Is Synjardy Used For?

The Food and Drug Administration (FDA) approved Synjardy for use in addition to diet and exercise to lower blood sugar in adults with type 2 diabetes. Because it contains empagliflozin, It also helps reduce the risk of cardiovascular death in people with diabetes and heart disease.

How to Take Synjardy

Take Synjardy as directed by your healthcare provider. How you take your medication will depend on whether you are prescribed the IR or XR formulation:

  • Synjardy IR tablet: Take twice daily by mouth with meals. Space your doses out by 12 hours.
  • Synjardy XR tablet: Take it by mouth once daily, with the first meal of the day. Do not crush, break, dissolve, or chew the tablet. Swallow it whole. Let your healthcare provider know if you have issues swallowing your pills.

Continue following your medication regimen even if you feel well.

Storage

The best place to store your pill is at room temperature (77 degrees F). But, during trips, you can keep Synjardy between cool and mildly hot temperatures (59 degrees F and 86 degrees F).

Store your drug in a dry place. Do not store this drug in your bathroom. Keep your pills away and out of reach from children and pets.

Throw out any unused or expired medicine. Do not flush it down the drain, kitchen sink, or toilet. Talk to your pharmacist about the best way to dispose of your leftover medication. Check out local take-back programs in your area.

How Long Does Synjardy Take to Work?

Synjardy starts to work within days after taking it. You can begin to see its full effects in two weeks. In clinical trials, there was a 2.1% mean A1c reduction from baseline at 24 weeks in people taking Synjardy as initial therapy.

What Are the Side Effects of Synjardy?

This is not a complete list of side effects and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 1-800-FDA-1088.

Common Side Effects

Some common side effects of Synjardy include but are not limited to:

Severe Side Effects

Synjardy can cause many serious side effects. Call your healthcare provider as soon as possible if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you have a medical emergency. Serious side effects can include the following:

A severe condition called lactic acidosis has happened while on this drug. Your risk increases if you are on metformin, drugs containing metformin, or if you have kidney or liver problems. It also increases with age.

Long-Term Side Effects

Long-term use of drugs with metformin is linked to vitamin B12 deficiency.

Report Side Effects

Synjardy may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your healthcare provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

Dosage: How Much of Synjardy Should I Take?

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The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For type 2 diabetes:
    • For oral dosage form (extended-release tablets):
      • Adults—At first, 1 or 2 tablets a day with food in the morning. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 25 mg of empagliflozin and 2000 mg of metformin per day.
      • Children—Use and dose must be determined by your doctor.
    • For oral dosage form (tablets):
      • Adults—At first, 1 tablet 2 times a day with food. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 25 milligrams (mg) of empagliflozin and 2000 mg of metformin per day.
      • Children—Use and dose must be determined by your doctor.

Modifications

Your healthcare provider may adjust your medication due to:

Age

Older people (65 and older) tolerate metformin well. But, lower and more conservative doses are safer in this population. Your healthcare provider may not prescribe the highest dose of metformin based on your age.

Bariatric Surgery 

Immediate-release tablets are recommended after having bariatric surgery. The extended-release pills do not work as well because of the bypass and increased bowel emptying.

Surgery

Your healthcare provider may tell you to stop taking your medication three to five days before undergoing surgery. This is to reduce the risk of a rare complication called euglycemic diabetic ketoacidosis. They will let you know when you can restart your treatment.

Veltassa Use

Veltassa is used to treat high levels of potassium in your blood. It can lower the level of metformin in your body. Take Synjardy at least three hours before or three hours after Veltassa.

Ranexa Use

Ranexa treats a heart condition called angina. It increases the levels of and the side effects of metformin. When taking metformin and Ranexa 1,000 milligrams twice daily, do not use more than 1,700 milligrams of metformin per day. Follow your healthcare provider's directions.

Diagnostic Tests

Iodinated contrast can make the side effects of metformin worse. It can affect the kidneys and cause lactic acidosis.

Metformin can lower the effect of the injection used in PET scans, making it more difficult for your healthcare provider to read the scans. Briefly stop metformin for at least 48 hours before your screening test, and monitor your blood sugar level regularly. Your healthcare provider will let you know when to restart your medication.

Pregnancy and Breastfeeding

Metformin crosses the placenta. Your healthcare provider may stop your medicine during your second and third trimesters. It may also be present in breast milk. Do not breastfeed while taking this drug due to the potential adverse effects on the nursing infant.

Missed Dose

Take your missed dose of Synjardy as soon as you remember. If it is too close to your next dose, skip the missed dose. Go back to your regular time. Do not double up or take extra doses. If you are not sure of what to do when you miss a dose, talk to your healthcare provider.

Overdose: What Happens If I Take Too Much Synjardy?

Overdose symptoms may include:

  • Fast or abnormal heartbeat
  • Confusion
  • Vomiting
  • Muscle pain and weakness

Overdoses of metformin have occurred with amounts greater than 50 grams. In some cases, overdosing on metformin can result in lactic acidosis.

What Happens If I Overdose on Synjardy?


If you think you or someone else may have overdosed on Synjardy, call a healthcare provider or the Poison Control Center (800-222-1222).

If someone collapses or isn't breathing after taking Synjardy, call 911 immediately.

Precautions

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It is very important that your doctor check your progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for unwanted effects.

Tell your doctor if you are pregnant or planning to become pregnant. It is not safe to take this medicine during the second and third trimester of pregnancy. It could harm an unborn baby. This medicine may cause some women who do not have regular monthly periods to ovulate. This can increase the chance of pregnancy if you are sexually active. If you are a woman of childbearing potential, you should discuss birth control options with your doctor.

Under certain conditions, too much metformin can cause a serious condition called lactic acidosis. Lactic acidosis usually occurs when other serious health problems are present, such as a heart attack or kidney failure. The symptoms of lactic acidosis include: stomach discomfort, decreased appetite, diarrhea, fast or shallow breathing, a general feeling of discomfort, muscle pain or cramping, and unusual sleepiness, tiredness, or weakness. If you have more than one of these symptoms together, you should get immediate emergency medical help.

Dizziness, lightheadedness, or fainting may occur with this medicine. This is more common if you have kidney disease, low blood pressure, or if you are taking a diuretic (water pill). Taking plenty of fluids each day may help. Drink plenty of water during exercise or in hot weather. Check with your doctor if you have severe nausea, vomiting, or diarrhea that does not stop. This may cause you to lose too much water.

Ketoacidosis (high ketones and acid in the blood) may occur while you are using this medicine. This can be life-threatening and requires immediate medical attention. Your doctor may give you insulin, fluid, and carbohydrate replacement to treat this condition. Tell your doctor right away if you have nausea, vomiting, trouble breathing, increased thirst or urination.

Tell your doctor if you have bloody urine, decrease in how much or how often you urinate, painful or difficult urination, lower back or side pain, fever, chills, or swelling of the face, finger, or lower legs. These may be symptoms of a serious kidney problem.

This medicine may cause serious allergic reactions, including angioedema, which can be life-threatening and require medical attention. Call your doctor right away if you have large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs while you are using this medicine.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine at least 3 days before having a major surgery or diagnostic tests, especially tests that use a contrast dye. This medicine may also affect the results of certain medical tests (eg, urine glucose tests may not be accurate).

This medicine may cause hypoglycemia (low blood sugar). This is more common when this medicine is taken together with other diabetes medicines (eg, insulin, glipizide, or glyburide). The symptoms of low blood sugar must be treated before they cause you to pass out. People feel different symptoms with low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Some symptoms of low blood sugar include: behavior changes that are similar to being drunk, blurred vision, cold sweats, confusion, cool, pale skin, difficulty with thinking, drowsiness, excessive hunger, a fast heartbeat, headaches that continue, nausea, shakiness, slurred speech, or unusual tiredness or weakness. Talk to your doctor about how to treat low blood sugar.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your diabetes medicine, overeat or do not follow your diet plan, have a fever or infection, or do not exercise as much as usual. High blood sugar can be very serious and must be treated right away. It is important that you learn which symptoms you have in order to treat it quickly. Talk to your doctor about the best way to treat high blood sugar.

This medicine may cause vaginal yeast infections in women and yeast infections of the penis in men. This is more common in patients who have a history of genital yeast infections or in men who are not circumcised. Women may have a vaginal discharge, itching, or odor. Men may have redness, itching, swelling, or pain around the penis, or a discharge with a strong odor from the penis. Check with your doctor right away if you have any of these symptoms.

This medicine may increase your risk of having urinary tract infections, including pyelonephritis or urosepsis. Check with your doctor right away if you have bladder pain, bloody or cloudy urine, difficult, burning, or painful urination, or lower back or side pain.

This medicine may cause a rare but serious bacterial infection, called necrotizing fasciitis of the perineum or Fournier's gangrene, which can cause damage to the tissue under the skin in the area between and around the anus and genitals (perineum). Fournier's gangrene may lead to hospitalization, multiple surgeries, or death. Check with your doctor right away if you have fever, unusual tiredness or weakness, or pain, tenderness, redness, or swelling of the area between and around your anus and genitals.

Limit the amount of alcohol you drink while you are using this medicine. Heavy alcohol use can increase your chances of serious side effects.

There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says you have diabetes with a list of all your medicines.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

What Are Reasons I Shouldn't Take Synjardy?

Do not take Synjardy if you:

  • Are on dialysis
  • Have severe kidney problems
  • Are allergic to empagliflozin, metformin, or any part of the formulation
  • Have metabolic acidosis (your body makes too much acid) or diabetic ketoacidosis (increased ketones in your blood or urine)

What Other Medications Interact With Synjardy?

Using Synjardy with some drugs can increase the risk of lactic acidosis. This includes:

  • Carbonic anhydrase inhibitors
  • Drugs that reduce metformin clearance, such as ranolazine, Tivicay (dolutegravir), and cimetidine
  • Alcohol

Other medications that can interact with Synjardy include:

This is not a complete list of drugs that might interact with Synjardy. Talk to your healthcare provider about all medications you take, including prescription and over-the-counter drugs, vitamins, and herbal supplements.

What Medications Are Similar?

Some combination drugs that are similar to Synjardy are:

  • Invokamet (canagliflozin and metformin)
  • Trijardy XR (empagliflozin, linagliptin, and metformin)
  • Metaglip (glipizide and metformin)
  • Glucovance (glyburide and metformin)
  • Janumet (sitagliptin and metformin)

These medications all have the drug metformin in common with Synjardy. They have similar side effects and interaction profiles as Synjardy. However, Trijardy XR (a combination of Synjardy and linagliptin) has more drug interactions and side effects.

This list is a list of drugs also prescribed for diabetes. It is NOT a list of drugs recommended to take with Synjardy. You should not take these drugs together. Ask your pharmacist or healthcare provider if you have any questions.

Frequently Asked Questions

  • What is Synjardy used for?

    Synjardy is used to help control blood sugar in adults with type 2 diabetes. It also reduces the chance of dying due to certain heart conditions.

  • What should I do if I miss a dose of Synjardy?

    Take your dose as soon as you think of it. Skip the missed dose if it is too close to the next dose. Return to your regular schedule. Do not double up or take extra doses.

  • How long should I briefly stop my medicine before a medical scan?

    Briefly stop taking your medicine at least 48 hours before a PET scan or scan with iodine contrast. Your healthcare provider will restart your drug when appropriate.

  • What are some side effects of Synjardy?

    Some common side effects of Synjardy are:

    • Gas
    • Upset stomach
    • Throwing up
    • Headache
    • Stomach pain
    • Feeling tired or weak
    • Diarrhea
    • Nose or throat irritation
  • How long does it take for Synjardy to work?

    Synjardy starts working in a few days. But, the full effect may be seen in two weeks.

How Can I Stay Healthy While Taking Synjardy?

Coping with type 2 diabetes may be stressful. However, when used in addition to a diet and exercise plan, Synjardy can help control your blood sugar.

If you have diabetes, it is important to regularly check your blood sugar. Make sure that your sugar level is always controlled. If your blood sugar is too low, call your healthcare provider right away. They may advise you to take liquid glucose, glucose tablets, or drink orange juice. Do not drive with low blood sugar.

Follow any diet plan that you discussed with your healthcare team. Do not take Synjardy with alcohol, and avoid caffeinated fluids. If you see something that looks like a pill in your stool, let your healthcare provider know.

Using this medicine long-term can cause low vitamin B12. This does not happen overnight, but rather with extended use. If you have any symptoms of low B12, talk to your healthcare provider. It would be best if you started treatment for B12 deficiency to resolve your symptoms.

This drug can harm a fetus if taken during pregnancy. Tell your healthcare provider if you become pregnant, plan to become pregnant or if you are breastfeeding.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended to replace medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

9 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. MedlinePlus. Empagliflozin.

  3. Food and Drug Administration. Synjardy XR label.

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  5. Pan D, Xu L, Chen P, et al. Empagliflozin in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials. Front Cardiovasc Med. 2021;8:683281. doi:10.3389/fcvm.2021.683281

  6. Lesko LJ, Offman E, Brew CT, et al. Evaluation of the potential for drug interactions with patiromer in healthy volunteers. J Cardiovasc Pharmacol Ther. 2017. doi:10.1177/1074248417691135

  7. Zack J, Berg J, Juan A, et al. Pharmacokinetic drug-drug interaction study of ranolazine and metformin in subjects with type 2 diabetes mellitus. Clin Pharmacol Drug Dev. 2015. doi:10.1002/cpdd.174

  8. Cho SY. To hold or not to hold metformin for FDG PET scans: that is the question. Radiology. 2018. doi:10.1148/radiol.2018181566

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By Queen Buyalos, PharmD
Queen Buyalos is a pharmacist and freelance medical writer. She takes pride in advocating for cancer prevention, overall health, and mental health education. Queen enjoys counseling and educating patients about drug therapy and translating complex ideas into simple language.