Insulin degludec and liraglutide

XULTOPHY® 100/3.6
(ZUL-to-fye)
(Insulin Degludec and Liraglutide Injection) for Subcutaneous Injection

Read this Medication Guide before you start using XULTOPHY 100/3.6 and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about XULTOPHY 100/3.6?

XULTOPHY 100/3.6 may cause serious side effects, including:

• Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rats and mice, liraglutide, one of the components of XULTOPHY 100/3.6, and medicines that work like liraglutide caused thyroid tumors, including thyroid cancer. It is not known if XULTOPHY 100/3.6 will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.
• Do not use XULTOPHY 100/3.6 if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

What is XULTOPHY 100/3.6?

XULTOPHY 100/3.6 is an injectable prescription medicine that contains 2 diabetes medicines, insulin degludec, 100 units/mL, and liraglutide, 3.6 mg/mL. XULTOPHY 100/3.6 should be used along with diet and exercise to lower blood sugar (glucose) in adults with type 2 diabetes mellitus when blood sugar levels are not well controlled on: 1) basal insulin (less than 50 units daily) or 2) liraglutide (less than or equal to 1.8 mg daily).

• XULTOPHY 100/3.6 is not recommended as the first choice of medicine for treating diabetes.
• It is not known if XULTOPHY 100/3.6 can be used in people who have had pancreatitis.
• XULTOPHY 100/3.6 is not recommended for use in combination with any other product containing liraglutide or another GLP-1 receptor agonist.
• XULTOPHY 100/3.6 is not for use in people with type 1 diabetes or people with diabetic ketoacidosis (increased ketones in the blood or urine).
• It is not known if XULTOPHY 100/3.6 can be used with mealtime insulin.
• It is not known if XULTOPHY 100/3.6 is safe and effective for use in children under 18 years of age.

Who should not use XULTOPHY 100/3.6?

Do not use XULTOPHY 100/3.6 if:

• you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• you are allergic to insulin degludec, liraglutide or any of the ingredients in XULTOPHY 100/3.6. See the end of this Medication Guide for a complete list of ingredients in XULTOPHY 100/3.6.
• you are having an episode of low blood sugar (hypoglycemia).

What should I tell my healthcare provider before using XULTOPHY 100/3.6?

Before using XULTOPHY 100/3.6, tell your healthcare provider about all your medical conditions, including if you:

• have or have had problems with your pancreas, kidneys, or liver.
• have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.
• are taking certain medicines called glucagon-like peptide 1 receptor agonists (GLP-1 receptor agonists).
• are pregnant or plan to become pregnant. It is not known if XULTOPHY 100/3.6 will harm your unborn baby. Tell your healthcare provider if you become pregnant while using XULTOPHY 100/3.6.
• are breastfeeding or plan to breastfeed. It is not known if XULTOPHY 100/3.6 passes into your breast milk. You should not use XULTOPHY 100/3.6 while breastfeeding.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. XULTOPHY 100/3.6 may affect the way some medicines work and some medicines may affect the way XULTOPHY 100/3.6 works. Before using XULTOPHY 100/3.6, talk to your healthcare provider about low blood sugar and how to manage it. Tell your healthcare provider if you are taking other medicines to treat diabetes. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I use XULTOPHY 100/3.6?

• Read the Instructions for Use that comes with XULTOPHY 100/3.6.
• Use XULTOPHY 100/3.6 exactly as your healthcare provider tells you to.
• Do not change your dosing schedule without first talking to your healthcare provider. The dose counter on your XULTOPHY 100/3.6 pen shows the number of units of XULTOPHY 100/3.6 to be injected.
• Your healthcare provider should show you how to use XULTOPHY 100/3.6 before you use it for the first time.
• XULTOPHY 100/3.6 is injected under the skin (subcutaneously) of your thigh, upper arm or stomach (abdomen).
• Do not inject XULTOPHY 100/3.6 into a muscle (intramuscularly) or vein (intravenously).
• Use XULTOPHY 100/3.6 at the same time each day with or without food.
• If you miss a dose of XULTOPHY 100/3.6, resume your 1 time daily dosing schedule at the next scheduled dose. Do not take 2 doses at the same time or increase your dose to make up for the missed dose. If you miss more than 3 days of XULTOPHY 100/3.6, call your healthcare provider for further instructions about taking XULTOPHY 100/3.6 at the right dose and to help lower your chance of having an upset stomach.
• Do not mix XULTOPHY 100/3.6 with any other insulin products or GLP-1 receptor agonists in the same injection.
• Check the Pen label each time you give your injection to make sure you are using the correct medication.
• Do not take more than 50 units of XULTOPHY 100/3.6 each day. XULTOPHY 100/3.6 contains two medicines: insulin degludec and liraglutide. If you take too much XULTOPHY 100/3.6, it can cause severe nausea and vomiting. Do not take XULTOPHY 100/3.6 with other GLP-1 receptor agonists. If you take too much XULTOPHY 100/3.6, call your healthcare provider or go to the nearest hospital emergency room right away.
• Change (rotate) your injection site with each injection to help reduce your chances of getting skin thickening or pits at the injection site. Do not use the same site for each injection.
• Do not share your XULTOPHY 100/3.6 pen with other people, even if the needle has been changed. You may give other people a serious infection or get a serious infection from them.

Check your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.

Your dose of XULTOPHY 100/3.6 and other diabetes medicines may need to change because of:

• change in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, or because of other medicines you take.

What should I avoid while taking XULTOPHY 100/3.6?

While taking XULTOPHY 100/3.6 do not:

• drive or operate heavy machinery, until you know how XULTOPHY 100/3.6 affects you.
• drink alcohol or use prescription or over-the-counter medicines that contain alcohol.

What are the possible side effects of XULTOPHY 100/3.6?

XULTOPHY 100/3.6 may cause serious side effects that can lead to death, including:

• See “What is the most important information I should know about XULTOPHY 100/3.6?”
• inflammation of your pancreas (pancreatitis). Stop using XULTOPHY 100/3.6 and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
• low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use XULTOPHY 100/3.6 with another medicine that can cause low blood sugar.

Signs and symptoms of low blood sugar may include:

• dizziness or light-headedness
• blurred vision
• anxiety, irritability, or mood changes
• sweating
• slurred speech
• hunger
• confusion or drowsiness
• shakiness
• weakness
• headache
• fast heartbeat
• feeling jittery
• kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems to get worse.
• serious allergic reactions. Stop using XULTOPHY 100/3.6 and get medical help right away, if you have any symptoms of a serious allergic reaction including itching, rash, or difficulty breathing.
• heart failure. Taking certain diabetes medicines called peroxisome proliferator-activated receptor (PPAR) gamma agonists or PPAR agonists with insulin containing products, including XULTOPHY 100/3.6, may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure, it may get worse while you take PPAR agonists with XULTOPHY 100/3.6. Your healthcare provider should monitor you closely while you are taking PPAR agonists with XULTOPHY 100/3.6. Tell your healthcare provider if you have any new or worse symptoms of heart failure including shortness of breath, tiredness, swelling of your ankles or feet and sudden weight gain. Treatment with PPAR agonists and XULTOPHY 100/3.6 may need to be adjusted or stopped by your healthcare provider if you have new or worse heart failure.
• low potassium in your blood (hypokalemia)

The most common side effects of XULTOPHY 100/3.6 may include stuffy or runny nose, sore throat, upper respiratory tract infection, increased blood levels of lipase, nausea, diarrhea, and headache. Talk to your healthcare provider about any side effect that bothers you or does not go away.

These are not all the possible side effects of XULTOPHY 100/3.6.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Keep XULTOPHY 100/3.6 and all medicines out of the reach of children.

General information about the safe and effective use of XULTOPHY 100/3.6.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use XULTOPHY 100/3.6 for a condition for which it was not prescribed. Do not give XULTOPHY 100/3.6 to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about XULTOPHY 100/3.6 that is written for healthcare professionals.

What are the ingredients in XULTOPHY 100/3.6?

Active Ingredients: insulin degludec and liraglutide

Inactive Ingredients: glycerol, phenol, zinc, and water for injection

Instructions for Use

XULTOPHY® 100/3.6
(ZUL-to-fye)
(insulin degludec and liraglutide injection)

• Do not share your XULTOPHY 100/3.6 pen with another person. You may give an infection to them or get an infection from them.
• XULTOPHY 100/3.6 pen (“pen”) is a prefilled disposable pen containing 300 units of insulin degludec and 10.8 mg of liraglutide (insulin degludec and liraglutide injection). You can inject doses from 10 to 50 units in a single injection (with each unit of insulin degludec, the pen also delivers 0.036 mg of liraglutide). The units can be increased by 1 unit at a time. The dose equals the number of units shown in the dose counter.
• This pen is not recommended for use by the blind or visually impaired without the assistance of a person trained in the proper use of the product.

Supplies you will need to give your XULTOPHY 100/3.6 injection:

• XULTOPHY 100/3.6 pen
• a new NovoFine or NovoTwist needle
• alcohol swab
• a sharps container for throwing away used pens and needles. See “After your injection” at the end of these instructions.

Preparing your XULTOPHY 100/3.6 pen:

• Wash your hands with soap and water.
• Before you start to prepare your injection, check the XULTOPHY 100/3.6 pen label before each use to make sure it is your XULTOPHY 100/3.6 pen.
• XULTOPHY 100/3.6 should look clear and colorless. Do not use XULTOPHY 100/3.6 if it is cloudy or colored.
• Do not use XULTOPHY 100/3.6 past the expiration date printed on the label or 21 days after you start using the pen.
• Always use a new needle for each injection to help ensure sterility and prevent blocked needles. Do not reuse or share needles with another person. You may give other people a serious infection or get a serious infection from them.

Figure A

Step 1:

• Pull pen cap straight off (See Figure B).

Figure B

Step 2:

• Check the liquid in the pen (See Figure C). XULTOPHY 100/3.6 should look clear and colorless. Do not use it if it looks cloudy or colored.

Figure C

Step 3:

• Select a new needle.
• Pull off the paper tab from the outer needle cap (See Figure D).

Figure D

Step 4:

• Push the capped needle straight onto the pen and twist the needle on until it is tight (See Figure E).

Figure E

Step 5:

• Pull off the outer needle cap. Do not throw it away (See Figure F).

Figure  F

Step 6:

• Pull off the inner needle cap and throw it away (See Figure G).

Figure G

Priming your XULTOPHY 100/3.6 pen:

Step 7:

• Turn the dose selector to select the priming symbol (..- ). (See Figure H).

Figure H

Step 8:

• Hold the pen with the needle pointing up. Tap the top of the pen gently a few times to let any air bubbles rise to the top (See Figure I).

Figure I

Step 9:

• Hold the pen with the needle pointing up. Press and hold in the dose button until the dose counter shows “0”. The “0” must line up with the dose pointer.
• A drop of XULTOPHY 100/3.6 should be seen at the needle tip (See Figure J).
  • If you do not see a drop of XULTOPHY 100/3.6, repeat steps 7 to 9, no more than 6 times, until a drop of XULTOPHY 100/3.6 appears at the needle tip.
  • If you still do not see a drop of XULTOPHY 100/3.6, change the needle and repeat steps 7 to 9.

Figure J

Selecting your dose: Make sure you prime your pen before setting your dose.

Step 10:

XULTOPHY 100/3.6 pen is made to deliver the number of units that your healthcare provider prescribed. Take your dose exactly as your healthcare provider tells you to. Do not change your dosing schedule without first talking to your healthcare provider.

• Turn the dose selector to select the dose you need to inject. The dose pointer should line up with your dose (See Figure K).
  • If you select the wrong dose, you can turn the dose selector forwards or backwards to the correct dose.
  • The even numbers are printed on the dial.
  • The odd numbers are shown as lines.

Figure K

• The XULTOPHY 100/3.6 pen scale will show you how much XULTOPHY 100/3.6 is left in your pen (See Figure L).

Figure L

• To see how much XULTOPHY 100/3.6 is left in your pen:
  • Turn the dose selector until it stops. The dose counter will line up with the dose that is left in your pen. If the dose counter shows 50, there is a dose of at least 50 units left in your pen.
  • If the dose counter shows between 10 and 50, the number shown in the dose counter is the total units left in your pen.
• If there is not enough XULTOPHY 100/3.6 left in your pen for a full dose, do not use it. Use a new XULTOPHY 100/3.6 pen.

Giving your injection:

• Inject your XULTOPHY 100/3.6 exactly as your healthcare provider has shown you. Your healthcare provider should tell you if you need to pinch the skin before injecting.
• XULTOPHY 100/3.6 can be injected under the skin (subcutaneously) of your stomach area (abdomen), upper legs (thighs) or upper arms.
• Change (rotate) your injection sites within the area you choose for each dose. Do not use the same injection site for each injection.

Step 11:

Choose your injection site and wipe the skin with an alcohol swab (See Figure M). Let the injection site dry before you inject your dose.

Figure M

Step 12:

• Insert the needle into your skin (See Figure N).
  • Make sure you can see the dose counter. Do not cover it with your fingers, this can stop your injection.

Figure N

Step 13:

• Press and hold down the dose button until the dose counter shows “0” (See Figure O).
  • The “0” must line up with the dose pointer. You may hear or feel a click.

Figure O

Step 14:

• Keep the needle in your skin after the dose counter has returned to “0” and slowly count to 6 (See Figure P).
  • When the dose counter returns to “0”, you will not get your full dose until 6 seconds later.
  • If the needle is removed before you count to 6, you may see a stream of XULTOPHY 100/3.6 coming from the needle tip.
  • If you see a stream of XULTOPHY 100/3.6 coming from the needle tip you will not get your full dose. If this happens you should check your blood sugar levels more often because you may need more XULTOPHY 100/3.6.

Figure P

Step 15:

• Pull the needle out of your skin (See Figure Q).
  • If you see blood after you take the needle out of your skin, press the injection site lightly with a piece of gauze or an alcohol swab. Do not rub the area.

Figure Q

Step 16:

• Carefully remove the needle from the pen after each use and throw it away (See Figure R).
  • Do not recap the needle. Recapping the needle can lead to needle stick injury.

Figure R

Note: If you do not have a sharps container, follow the steps below:

• Carefully slip the needle into the outer needle cap (See Figure S). Safely remove the needle and throw it away as soon as you can.
  • Do not store the pen with the needle attached. Storing without the needle attached helps prevent leaking, blocking of the needle, and air from entering the pen.

Figure S

Step 17:

• Replace the pen cap by pushing it straight on (See Figure T).

Figure T

After your injection:

• Put your used XULTOPHY 100/3.6 pen and needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and pens in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic
  • can be closed with a tight-fitting, puncture resistant lid, without sharps being able to come out
  • upright and stable during use
  • leak-resistant
  • properly labeled to warn of hazardous waste inside the container
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about the safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

How should I store my XULTOPHY 100/3.6 pen?

Before use:

• Store unused XULTOPHY 100/3.6 pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze XULTOPHY 100/3.6. Do not use XULTOPHY 100/3.6 if it has been frozen.
• Unused pens may be used until the expiration date printed on the label, if kept in the refrigerator.
• If XULTOPHY 100/3.6 is stored outside of refrigeration prior to first use, it should be used or thrown away within 21 days.
• Store the pens in the carton they come in to keep them clean and protected from light.

Pen in use:

• Store the pen you are currently using out of the refrigerator below 86°F (30°C) or in a refrigerator at 36°F to 46°F (2°C to 8°C).
• Do not freeze XULTOPHY 100/3.6. Do not use XULTOPHY 100/3.6 if it has been frozen.
• Keep XULTOPHY 100/3.6 away from heat or light.
• The XULTOPHY 100/3.6 pen you are using should be thrown away after 21 days, even if it still has XULTOPHY 100/3.6 left in it and the expiration date has not passed.

General Information about the safe and effective use of XULTOPHY 100/3.6.

• Keep XULTOPHY 100/3.6 pens and needles out of the reach of children.
• Always use a new needle for each injection.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Get emergency medical help if you have signs of an allergic reaction: 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--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may 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.

• If you have an allergy to this medicine or any part of insulin degludec and liraglutide.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Acidic blood problem or type 1 diabetes.
• If you have low blood sugar.
• If you are using insulin.
• If you are using another drug that has the same drug in it.
• If you are using any of these drugs: Albiglutide, dulaglutide, exenatide, or lixisenatide.
• If you are breast-feeding. Do not breast-feed while you take this medicine.

This is not a list of all drugs or health problems that interact with insulin degludec and liraglutide.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take insulin degludec and liraglutide. This includes your doctors, nurses, pharmacists, and dentists.
• Allergic reactions have happened with this medicine. Rarely, some reactions can be very bad or life-threatening. Talk with the doctor.
• Low blood sugar may happen with insulin degludec and liraglutide. Very low blood sugar can lead to seizures, passing out, long lasting brain damage, and sometimes death. Talk with the doctor.
• Low blood potassium may happen with this medicine. If not treated, this can lead to a heartbeat that is not normal, very bad breathing problems, and sometimes death. Talk with the doctor.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how insulin degludec and liraglutide affects you.
• Some diabetes drugs like pioglitazone or rosiglitazone may cause heart failure or make it worse in people who already have it. Using insulin with these drugs may increase this risk. If you also take one of these drugs, talk with the doctor.
• It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
• Wear disease medical alert ID (identification).
• Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
• Check your blood sugar as you have been told by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Avoid drinking alcohol or taking products that have alcohol in them while taking this medicine.
• Do not share pen or cartridge devices with another person even if the needle has been changed. Sharing these devices may pass infections from one person to another. This includes infections you may not know you have.
• A very bad and sometimes deadly pancreas problem (pancreatitis) has happened with insulin degludec and liraglutide. Talk with your doctor.
• Kidney problems have happened with this medicine. Sometimes, kidney problems may need to be treated in the hospital. Dialysis may also be needed. Talk with your doctor.
• If you cannot drink liquids by mouth or if you have upset stomach, throwing up, or diarrhea that does not go away, you need to avoid getting dehydrated. Contact your doctor to find out what to do. Dehydration may lead to new or worse kidney problems.
• If you are 65 or older, use insulin degludec and liraglutide with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

• Store unopened pens in a refrigerator. Do not freeze.
• Store in original container.
• Do not use if it has been frozen.
• After first use, store in a refrigerator or at room temperature. Protect from heat and light. Throw away any part not used after 3 weeks.
• Take off the needle after each shot. Do not store this device with the needle on it.
• Keep the cap on the pen when not in use.
• Do not use if this medicine is out of date.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• Xultophy

Hypersensitivity to insulin degludec, liraglutide, or any component of the formulation; history of or family history of medullary thyroid carcinoma (MTC); patients with multiple endocrine neoplasia syndrome type 2 (MEN2); during episodes of hypoglycemia

Diabetes mellitus, type 2: SubQ: Note: Alternative antidiabetic agents should be used if patient persistently requires dosages <16 units or requires dosages >50 units.

Initial: 16 units (insulin degludec 16 units/liraglutide 0.58 mg) once daily; titrate dose upward or downward every 3 to 4 days in increments of 2 units (insulin degludec 2 units/liraglutide 0.072 mg) per glycemic response. Usual range: 16 units (insulin degludec 16 units/liraglutide 0.58 mg) to 50 units (insulin degludec 50 units/liraglutide 1.8 mg) once daily; if necessary, dose may be temporarily titrated down to 10 to 15 units (insulin degludec 10 to 15 units/liraglutide 0.36 to 0.54 mg) once daily. Maximum dose: 50 units (insulin degludec 50 units/liraglutide 1.8 mg)/day

Missed dose: Resume with next regularly scheduled dose; do not administer an extra dose or increase dose to account for missed dose. If more than 3 days have elapsed since last dose, reinitiate at the initial dosage (insulin degludec 16 units/liraglutide 0.58 mg) once daily

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Insulin. Exceptions: Levobunolol; Metipranolol. Monitor therapy

DPP-IV Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

GLP-1 Agonists: May enhance the hypoglycemic effect of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Exceptions: Liraglutide. Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulin: Liraglutide may enhance the hypoglycemic effect of Insulin. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification

Liraglutide: May enhance the hypoglycemic effect of Insulin. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Metreleptin: May enhance the hypoglycemic effect of Insulin. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pioglitazone: May enhance the adverse/toxic effect of Insulin. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, dose reductions should be considered to reduce the risk of hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure. Consider therapy modification

Pramlintide: May enhance the hypoglycemic effect of Insulin. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Rosiglitazone: Insulin may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

SGLT2 Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Sulfonylureas: GLP-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Individualize dose in accordance with patient's needs.
-Discontinue both liraglutide and basal insulin prior to initiation with this combination product.
-This drug is prescribed in dose steps: One dose step provides insulin degludec 1 unit plus liraglutide 0.036 mg; the dose counter on pen shows dose steps
-Maximum daily dose: 50 dose steps (insulin degludec 50 units-liraglutide 1.8 mg)

-Initial dose: 16 dose steps (insulin degludec 16 units-liraglutide 0.58 mg) subcutaneously once a day
-Titrate up or down by 2 units every 3 to 4 days based on metabolic needs, blood glucose monitoring results, and glycemic control goal until the desired fasting plasma glucose is achieved.
-Maintenance dose: 16 to 50 units (dose steps) subcutaneously once a day
-Maximum daily dose: 50 units (50 dose steps: insulin degludec 50 units-liraglutide 1.8 mg)

Comments:
-This combination drug is not recommended as first-line therapy because of the uncertain relevance of the rodent C-cell tumor finding to humans.
-This drug should not be used in combination with any other product containing liraglutide or another GLP-1 receptor agonist.
-The combination drug has not been studied in combination with prandial insulin.
-Alternative antidiabetic therapy should be considered if patients require a daily dose persistently below 16 units per day or over 50 units per day.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes inadequately controlled on basal insulin (less than 50 units per day) or liraglutide (less than or equal to 1.8 mg per day).