Xultophy is an injection pen containing a combination of insulin degludec and liraglutide. Insulin degludec is a long-acting insulin that starts to work several hours after injection and keeps working evenly for 24 hours.

Liraglutide is similar to a hormone that occurs naturally in the body and helps control blood sugar, insulin levels, and digestion.

Xultophy is used to lower blood sugar in adults with type 2 diabetes mellitus. This medicine should be used together with diet and exercise.

Xultophy is usually given when your blood sugar levels have not been well controlled by using other medications.

Xultophy is not for people with type 1 diabetes.

You should not use Xultophy if you have multiple endocrine neoplasia type 2 (tumors in your glands), a personal or family history of medullary thyroid cancer, insulin-dependent diabetes, or if you are having an episode of low blood sugar or diabetic ketoacidosis.

In animal studies, liraglutide caused thyroid tumors or thyroid cancer. It is not known whether these effects would occur in people.

Call your doctor at once if you have signs of a thyroid tumor, such as swelling or a lump in your neck, trouble swallowing, a hoarse voice, or shortness of breath.

Before taking this medicine

You should not use Xultophy if you are allergic to insulin or liraglutide. Do not use this medicine during an episode of low blood sugar, or if you have:

• multiple endocrine neoplasia type 2 (tumors in your glands);

• a personal or family history of medullary thyroid carcinoma (a type of thyroid cancer);

• diabetic ketoacidosis (call your doctor for treatment); or

• a condition for which you use liraglutide (Saxenda, Victoza) or a medicine like liraglutide (albiglutide, dulaglutide, exenatide, lixisenatide, Adlyxin, Byetta, Bydureon, Tanzeum, Trulicity).

To make sure Xultophy is safe for you, tell your doctor if you have ever had:

• pancreatitis;

• kidney or liver disease;

• stomach problems causing slow digestion;

• alcoholism;

• gallstones; or

• if you also use a meal-time insulin.

In animal studies, liraglutide caused thyroid tumors or thyroid cancer. It is not known whether these effects would occur in people using regular doses. Ask your doctor about your risk.

Tell your doctor if you are pregnant or breastfeeding.

Follow your doctor's instructions about using insulin if you are pregnant or you become pregnant. Controlling diabetes is very important during pregnancy, and having high blood sugar may cause complications in both the mother and the baby.

Xultophy is not approved for use by anyone younger than 18 years old.

Use Xultophy exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Xultophy is injected under the skin, usually once daily at the same time each day. A healthcare provider will teach you how to properly use the medication by yourself. Use only the injection pen supplied with this medicine. Do not dilute or mix other medicines in the injection with Xultophy.

You may use Xultophy with or without food.

Your care provider will show you the best places on your body to inject this medicine. Use a different place each time you give an injection. Do not inject into the same place two times in a row.

Do not inject Xultophy into skin that is damaged, tender, bruised, pitted, thickened, scaly, or has a scar or hard lump.

Call your doctor if you have ongoing vomiting or diarrhea. You can easily become dehydrated while using Xultophy which lead to kidney failure.

Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office.

You may have low blood sugar (hypoglycemia) and feel very hungry, dizzy, irritable, confused, anxious, or shaky. To quickly treat hypoglycemia, eat or drink a fast-acting source of sugar (fruit juice, hard candy, crackers, raisins, or non-diet soda).

Your doctor may prescribe a glucagon injection kit in case you have severe hypoglycemia. Be sure your family or close friends know how to give you this injection in an emergency.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your dose or medication schedule.

Never share an Xultophy injection pen with another person, even if the needle has been changed. Sharing these devices can allow infections or disease to pass from one person to another.

Keep Xultophy in its original container protected from heat and light. Do not freeze insulin or store it near the cooling element in a refrigerator. Throw away any insulin that has been frozen.

Storing unopened (not in use) Xultophy:

• Refrigerate and use until expiration date; or

• Store at room temperature and use within 21 days (3 weeks).

Storing opened (in use) Xultophy:

• Store at room temperature away from heat and light, and use within 21 days; or

• Store in a refrigerator and use within 21 days.

Do not store the injection pen with a needle attached.

Do not use the medicine if it looks cloudy or has changed colors. Call your pharmacist for new medicine.

Usual Adult Dose of Xultophy for Diabetes Type 2:

Basal Insulin or GLP-1 Receptor Agonist Naive:
Initial dose: 10 units subcutaneously once a day

Currently receiving a Basal Insulin or GLP-1 Receptor Agonist
-Discontinue therapy with basal insulin and/or liraglutide
Initial dose: 16 units subcutaneously once a day

TITRATION: Adjust dose up or down in increments of 2 units every 3 to 4 days based on individual metabolic needs, blood glucose monitoring, and glycemic goal until desired fasting plasma glucose is achieved
Maximum daily dose: 50 units (insulin degludec 50 units; liraglutide 1.8 mg)

Comments:
-Dosing is provided as insulin degludec units; the liraglutide component dose for each unit of insulin degludec is displayed on a dosing table in the package labeling; 10 units of insulin degludec provides 0.36 mg of liraglutide.
-To minimize the risk of hypoglycemia or hyperglycemia, additional titration may be necessary with changes in physical activity, food intake, during acute illness, or with use of concomitant medications.
-This combination drug is not recommended as first-line therapy because of the uncertainty of rodent C-cell tumor finding to humans.
-The combination drug has not been studied in combination with prandial insulin.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

You should not use Xultophy if you are allergic to insulin or liraglutide. Do not use this medicine during an episode of low blood sugar, or if you have:

• multiple endocrine neoplasia type 2 (tumors in your glands);

• a personal or family history of medullary thyroid carcinoma (a type of thyroid cancer);

• diabetic ketoacidosis (call your doctor for treatment); or

• a condition for which you use liraglutide (Saxenda, Victoza) or a medicine like liraglutide (albiglutide, dulaglutide, exenatide, lixisenatide, Adlyxin, Byetta, Bydureon, Tanzeum, Trulicity).

To make sure Xultophy is safe for you, tell your doctor if you have ever had:

• pancreatitis;

• kidney or liver disease;

• stomach problems causing slow digestion;

• alcoholism;

• gallstones; or

• if you also use a meal-time insulin.

In animal studies, liraglutide caused thyroid tumors or thyroid cancer. It is not known whether these effects would occur in people using regular doses. Ask your doctor about your risk.

Tell your doctor if you are pregnant or breastfeeding.

Follow your doctor's instructions about using insulin if you are pregnant or you become pregnant. Controlling diabetes is very important during pregnancy, and having high blood sugar may cause complications in both the mother and the baby.

Xultophy is not approved for use by anyone younger than 18 years old.

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

If you miss your dose for more than 3 days in a row, call your doctor for instructions.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. You should not use more than 50 units of this medicine in one day.

Do not drink alcohol. Check your other medicine labels to be sure these products do not contain alcohol.

Avoid driving or hazardous activity until you know how this medicine will affect you. Your reactions could be impaired.

Get emergency medical help if you have signs of an allergic reaction to Xultophy: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe nausea and vomiting;

• shortness of breath (even with mild exertion);

• swelling in your feet or ankles, rapid weight gain;

• signs of pancreatitis - severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

• kidney problems - little or no urination, painful or difficult urination; or

• low potassium level - leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common Xultophy side effects include:

• nausea, diarrhea;

• headache; or

• cold symptoms such as stuffy or runny nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Many other medicines can affect your blood sugar, and some medicines can increase or decrease the effects of Xultophy. Some drugs can also cause you to have fewer symptoms of hypoglycemia, making it harder to tell when your blood sugar is low. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. This includes prescription and over-the-counter medicines, vitamins, and herbal products.