Glyxambi (Empagliflozin and Linagliptin) - Oral

What Is Glyxambi?

Glyxambi (empagliflozin and linagliptin) is a prescription drug used along with diet and exercise to control blood sugar in adults with type 2 diabetes. It also lowers the risk of heart-related death in adults with type 2 diabetes and heart disease.

Glyxambi contains two drugs: empagliflozin and linagliptin. Empagliflozin is in a drug class called sodium-glucose cotransporter 2 (SGLT2) inhibitors. Linagliptin is in a drug class called dipeptidyl peptidase 4 (DPP-4) inhibitors, also known as gliptins.

Combining these two medications lowers blood sugar levels and helps the body eliminate sugar. It also allows the body to produce more insulin (which lowers blood sugar levels) and decreases glucagon. Since glucagon increases blood sugar, blood sugar levels are better controlled by decreasing glucagon.

Glyxambi is available as an oral tablet that is taken by mouth.

What Is Glyxambi Used For?

The Food and Drug Administration (FDA) approved Glyxambi to:

• Improve blood sugar levels (in combination with diet and exercise) in adults with type 2 diabetes.  
• Lower the risk of cardiovascular (heart-related) death in adults with both type 2 diabetes and established heart disease.

Glyxambi is not indicated for use in type 1 diabetes due to its ability to increase the risk of diabetic ketoacidosis (DKA) when used in this population. DKA is a life-threatening complication of diabetes that can occur when the body makes high levels of blood acids (ketones). DKA more commonly occurs in people with type 1 diabetes than in people with type 2 diabetes.

Glyxambi has not been studied in people who have a history of pancreatitis (inflammation of the pancreas).

How to Take Glyxambi

Before taking Glyxambi, read the information leaflet that comes with your prescription. Consult your healthcare provider with any questions or concerns. Take Glyxambi exactly as your healthcare provider instructed, usually once daily in the morning, with or without food. Do not skip doses or change the amount taken unless required.

Your healthcare provider may prescribe Glyxambi with or without other diabetes medications. Low blood sugar episodes are more likely when taking Glyxambi with certain other diabetes drugs, so ask about testing blood sugar and ketones, hypoglycemia (low blood sugar), and how to treat it.

Moreover, empagliflozin, one of the ingredients in Glyxambi, can cause life-threatening ketoacidosis. Your healthcare provider may order blood work to test your kidney function before and during Glyxambi treatment. While on treatment, notify your healthcare provider if you become sick with diarrhea or vomiting, are dehydrated, experience trauma, or have an upcoming surgery—all factors which can affect blood sugar.

And while taking your medication, follow the general guidelines for a healthy lifestyle, including eatomg a well-balanced diet and exercising.

Storage

Store Glyxambi at room temperature (68–77 degrees Fahrenheit), away from heat, direct light, and moisture. Do not keep this medication in the bathroom; store it in its original labeled container and keep it out of reach of children and pets. Make sure the lid is tightly closed when not in use.

What Are the Side Effects of Glyxambi?

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 800-FDA-1088.

Common Side Effects

The most common side effects of Glyxambi are:

• Urinary tract infection (UTI)
• Increased urination
• Genital mycotic infection (fungal infection of the genitals)
• Common cold/cough/upper respiratory infection
• Hypoglycemia
• High cholesterol
• Nausea and diarrhea
• Joint pain

The most common lab abnormalities associated with taking Glyxambi include:

• Hyperuricemia (increased uric acid levels in the blood)
• Hyperlipasemia (increased levels of the pancreatic enzyme lipase in the blood, which could signal a problem with the pancreas)
• Increased levels of creatinine, which could indicate kidney problems
• Increased hematocrit (excess red blood cells)

Severe Side Effects

Call your healthcare provider immediately if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Hypersensitivity reaction or anaphylaxis: Symptoms can include rash, hives, difficulty breathing, and swelling around the lips, tongue, and face. An allergic reaction may require emergency medical attention. 
• Angioedema: Characterized by swelling under the skin, this adverse effect also requires emergency medical attention.
• Hypoglycemia
• Heart failure: Call your healthcare provider right away if you have symptoms of swelling, shortness of breath, or rapid weight gain.
• Pancreatitis (an inflamed pancreas, which can be life-threatening): Call your healthcare provider right away if you have pain in the upper stomach area that may spread to the back, with or without vomiting.
• Severe joint pain: Call your healthcare provider right away if you have joint pain that is severe or ongoing.
• Rhabdomyolysis (muscle breakdown which can cause kidney damage)
• Bullous pemphigoid (a rare skin condition that can cause blisters filled with fluid): Call your healthcare provider right away if you have itching, blisters, or a breakdown of the outer layer of the skin. 
• Serious UTI: Consult your healthcare provider if you have symptoms of a serious UTI, which can include pain or burning when you urinate, blood in the urine, and/or stomach or back pain.
• Ketoacidosis: Get medical help right away if you have nausea, vomiting, stomach pain, confusion, extreme drowsiness, or difficulty breathing.
• Kidney injury
• Orthostatic hypotension (a drop in blood pressure when you stand up from a sitting or lying down position): Consult your healthcare provider if you feel light-headed.
• Fournier’s gangrene: Get medical attention right away if you have pain/tenderness, redness, or swelling of the genitals or the area from the genitals to the rectum, fever, or discomfort. These symptoms can worsen quickly and can become life-threatening.

Long-Term Side Effects

Long-term or delayed side effects are possible. Some long-term or delayed side effects can be mild, such as:

• Weight loss
• Cough
• Joint pain
• Sore throat
• Infection

Moderate long-term or delayed side effects may include:

• High cholesterol
• Fungal infections (including genital fungal infections)
• UTI
• Dehydration
• Orthostatic hypotension
• Mouth sores/ulcers

Severe long-term or delayed side effects may include:

• Kidney failure
• Pancreatitis
• Severe skin reactions
• Diabetic ketoacidosis
• Heart failure
• Muscle breakdown which can lead to kidney damage
• Necrotizing fasciitis of the perineum: This necrotizing fasciitis is also called Fournier’s gangrene and can be life-threatening, causing symptoms such as pain, redness, and swelling in the genital and perianal area. Severe side effects require immediate medical attention.

Dosage: How Much Glyxambi Should I Take?

Modifications

Due to the possible effects of this medication, there may be changes to how it is used. Therefore, it is important for users to be aware of the following when taking Glyxambi.

Pregnancy: Glyxambi should not be used in the second and third trimesters of pregnancy due to the potential risk to the fetus. Glyxambi is generally not used during the first trimester. If you already take Glyxambi and find out you are pregnant, consult your healthcare provider.

Breastfeeding: Glyxambi is generally not recommended while breastfeeding. Consult your healthcare provider for advice. 

Older adults: Adults age 65 and older (as well as adults with kidney problems or who take medications called loop diuretics) are at higher risk for dehydration or low blood pressure from Glyxambi.

People with liver problems: No dosage adjustment is required for adults with liver problems.

People with kidney problems: People with kidney problems are at higher risk of dehydration or low blood pressure, as well as UTIs when taking Glyxambi. Glyxambi should not be used in people who are on dialysis or who have an eGFR of less than 30 (eGFR is a measure of kidney function that stands for estimated glomerular filtration rate).

Missed Dose

Take Glyxambi as prescribed by your healthcare provider. If you miss a dose, take it as soon as you can. If it is almost time for the next dose, skip the missed dose. Do not take two doses together.

Overdose: What Happens If I Take Too Much Glyxambi?

Contact your healthcare provider or the Poison Control Center if you think you may have overdosed on Glyxambi. Call 911 if someone collapses, has a seizure or difficulty speaking, or can't breathe or wake up after taking their medication.

Precautions

What Are Reasons I Shouldn’t Take Glyxambi?

Glyxambi is not appropriate for everyone. There are certain reasons your healthcare provider may not prescribe this medication for you.

You should not take this medication if you are allergic to empagliflozin, linagliptin, any inactive ingredients in Glyxambi, or any drug in the SGLT2 inhibitor or DPP-4 inhibitor drug class.

You may not be prescribed Glyxambi if any of the following apply to you:

• Allergy to empagliflozin, linagliptin, inactive ingredients in Glyxambi, or any drug in the SGLT2 inhibitor or DPP-4 inhibitor drug class. Let your healthcare provider know if you have had an allergic reaction to any of these drugs previously.
• Second or third trimester of pregnancy
• Type 1 diabetes
• Volume depletion or dehydration
• An eGFR less than 30

Glyxambi may be prescribed with caution in some people only if their healthcare provider determines it is safe. These populations include:

• People with an eGFR between 30 and 59
• People who take medications that may harm the kidneys
• People with low blood pressure 
• Older adults
• People at risk for heart failure, pancreatitis, or ketoacidosis
• People with insulin deficiency
• People who have fasted for a prolonged time
• People with alcohol use disorder or who misuse alcohol
• People with a history of UTIs or genital fungal infections
• Uncircumcised males

What Other Medications May Interact With Glyxambi?

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter (OTC) medicines, and vitamins or supplements.

Glyxambi can interact with:

• Diuretics such as hydrochlorothiazide or Lasix (furosemide)
• Insulin 
• Insulin secretagogues, which include Amaryl (glimepiride), Glucotrol (glipizide), glyburide, repaglinide, and nateglinide
• Rifadin (rifampin) 
• Seizure medications such as Dilantin (phenytoin), phenobarbital, and Tegretol (carbamazepine) 
• Saint-John’s-wort

Other drug interactions may occur with Glyxambi. Consult your healthcare provider for a full list of drug interactions.

What Medications Are Similar?

Glyxambi contains two drugs: empagliflozin and linagliptin.

Empagliflozin is an SGLT2 inhibitor. It is also available as the single-ingredient drug Jardiance, which has only empagliflozin. Other SGLT2 inhibitors include:

• Invokana (canagliflozin)
• Farxiga (dapagliflozin) 
• Steglatro (ertugliflozin)

Empagliflozin is also available as part of other combination products in addition to Glyxambi, such as:

• Synjardy and Synjardy XR (empagliflozin and metformin)
• Trijardy XR (linagliptin, empagliflozin, and metformin)

Linagliptin, the second ingredient in Glyxambi, is a DPP-4 inhibitor. It is available as the single-ingredient drug Tradjenta, which contains linagliptin only. Other drugs in this class include:

• Januvia (sitagliptin)
• Nesina (alogliptin)
• Onglyza (saxagliptin)

Linagliptin is also available as part of a combination product in the following drugs, in addition to Glyxambi:

• Jentadueto and Jentadueto XR (linagliptin and metformin)
• Trijardy XR (linagliptin, empagliflozin, and metformin)

Other oral medications are available to help control blood sugar in adults with type 2 diabetes, such as:

• Glinides: Repaglinide, nateglinide
• Glucophage (metformin)
• Sulfonylureas: Amaryl (glimepiride), Glucotrol (glipizide), and glyburide
• Thiazolidinediones: Actos (pioglitazone)

Some people with type 2 diabetes use injectable medications that are not insulin but that also help control blood glucose levels. These drugs are part of a class called glucagon-like peptide-1 (GLP-1) agonists. Examples of these drugs are:

• Ozempic (semaglutide)
• Saxenda (liraglutide)
• Trulicity (dulaglutide)
• Victoza (liraglutide)

There is also one oral GLP-1 agonist available, called Rybelsus (semaglutide).

People with type 2 diabetes may also need injectable insulin to help control blood glucose. There are different types of short-acting insulin and long-acting insulin. Examples of short-acting insulin include Humalog (insulin lispro) and Novolog (insulin aspart). Examples of long-acting insulin include Lantus (insulin glargine) and Levemir (insulin detemir).

The above is a list of drugs also prescribed for type 2 diabetes. It is not necessarily a list of drugs recommended to take with Glyxambi. Your healthcare team will work with you to find the best treatment regimen for controlling your blood sugar.

How Can I Stay Healthy While Taking Glyxambi?

Before taking Glyxambi, discuss your medical history and medications with your healthcare provider. When taking Glyxambi, follow your healthcare provider’s instructions for use. Read the patient information that comes with your prescription. Consult your healthcare provider if you have any questions.

Ask your healthcare provider if you should carry glucagon with you. Glucagon can raise blood sugar in a severely low blood sugar emergency (when you are unable to eat or drink). Glucagon is available by injection or as a nasal spray called Baqsimi. Ensure your loved ones, friends, or caregivers know how to use it in an emergency.

Glyxambi is meant to be used along with a diet and exercise plan for controlling your blood sugar. Work with your healthcare team to devise the best plan for your needs. A registered dietitian may be a helpful resource for this.

Your healthcare provider will advise you on how often to check your blood sugar levels. Check to see if your provider's office has a certified diabetes care and education specialist who can teach you how to use your meter and answer questions about disease management.

Another helpful tip for people with diabetes is to purchase a medical alert device and wear it at all times. This will alert emergency responders that you have type 2 diabetes. Additionally, keep a few essential items on hand at all times. Pack these in a diabetes kit or supplies bag:

• Blood glucose testing meter and extra supplies such as strips, lancing device, lancets, alcohol wipes, and batteries
• Emergency contact information
• Glucagon (injection or nasal spray) 
• Low blood sugar treatments such as juice boxes, glucose tablets, honey sticks, and Smarties