Xultophy

Primary Use

Xultophy is used to help manage blood sugar levels in adults with type 2 diabetes mellitus. It is a combination of two different types of medications: a long-acting insulin and a glucagon-like peptide-1 (GLP-1) receptor agonist. These components work together to help the body regulate glucose throughout the day.

When It Is Prescribed

Healthcare providers typically prescribe Xultophy when a patient's blood sugar remains high despite using other diabetes treatments. It is often used when diet, exercise, and other oral or injectable medications have not provided enough glycemic control on their own.

Limitations of Use

While Xultophy is effective for type 2 diabetes, there are specific situations where it is not appropriate:

• Type 1 Diabetes: It is not used to treat type 1 diabetes.
• Diabetic Ketoacidosis: It should not be used to treat diabetic ketoacidosis, a serious condition involving high levels of ketones in the blood or urine.
• Pancreatitis History: It has not been studied in people who have had inflammation of the pancreas (pancreatitis).
• Other GLP-1 Medications: It is not recommended for use in combination with other GLP-1 receptor agonists.

How Xultophy Works

Xultophy contains two active ingredients that work together to control blood sugar: insulin degludec and liraglutide.

Insulin Degludec

Insulin degludec is a long-acting (basal) insulin. It works by replacing the insulin that the body would normally produce. Its primary functions include:

• Helping cells in the muscles and fat take in sugar from the bloodstream to use as energy.
• Reducing the amount of sugar the liver produces and releases into the blood.

Because it is long-acting, it provides a steady level of insulin in the body for an extended period.

Liraglutide

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It mimics a natural hormone in the body to manage blood sugar in several ways:

• Increasing insulin release: It signals the pancreas to release more insulin, but only when blood sugar levels are high.
• Lowering glucagon: It reduces the secretion of glucagon, a hormone that tells the liver to release stored sugar.
• Slowing digestion: It slows down the speed at which food leaves the stomach, which helps prevent blood sugar from rising too quickly after a meal.

Common Side Effects

Many people using Xultophy experience mild side effects that may improve as the body adjusts to the medication. The most frequently reported symptoms include:

• Nausea and diarrhea
• Headache
• Upper respiratory tract infections (such as a sore throat or runny nose)
• Increased levels of lipase (a digestive enzyme)

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Contact a healthcare provider right away if you experience any of the following:

Low Blood Sugar (Hypoglycemia)

Because Xultophy contains insulin, it can cause blood sugar levels to drop too low. Signs of hypoglycemia include dizziness, sweating, confusion, shakiness, and blurred vision.

Pancreatitis

This medication may cause inflammation of the pancreas. Symptoms include severe pain in the stomach area that may spread to the back, with or without vomiting.

Kidney and Gallbladder Problems

Severe nausea or diarrhea can lead to dehydration, which may cause kidney failure. Additionally, some users may develop gallbladder issues, such as gallstones or inflammation, which can cause pain in the upper right stomach area.

Thyroid Tumors

One of the components in Xultophy has been linked to a risk of thyroid tumors. Tell your doctor if you notice a lump or swelling in your neck, hoarseness, or difficulty swallowing.

Severe Allergic Reactions

Seek emergency help if you experience signs of a serious allergic reaction, such as swelling of the face, lips, or tongue, difficulty breathing, or a rapid heartbeat.

Thyroid Tumor Risk

Xultophy contains liraglutide, which has caused thyroid C-cell tumors in animal studies. It is unknown if this medication causes these tumors in humans. Xultophy is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Pancreatitis

Inflammation of the pancreas (pancreatitis) has been reported in clinical trials. Patients should be monitored for signs such as persistent, severe abdominal pain that may radiate to the back. If pancreatitis is suspected, the medication should be discontinued.

Hypoglycemia

Low blood sugar (hypoglycemia) is the most common side effect and can be life-threatening. The risk increases with changes in dose, meal patterns, or the addition of other glucose-lowering medications. Severe hypoglycemia can lead to seizures, unconsciousness, or death.

Kidney and Gallbladder Disease

There have been reports of acute kidney injury and worsening of chronic renal failure, sometimes requiring hemodialysis. Dehydration resulting from gastrointestinal side effects may contribute to kidney problems. Additionally, gallbladder problems such as gallstones or gallbladder inflammation have occurred in patients taking this medication.

Other Warnings and Precautions

• Severe Allergic Reactions: Serious hypersensitivity reactions, including anaphylaxis and angioedema, can occur.
• Heart Failure: Using Xultophy in combination with thiazolidinediones (TZDs) may cause fluid retention, which can lead to new or worsening heart failure.
• Low Potassium: All insulin-containing products can cause a shift in potassium levels, potentially leading to hypokalemia. If left untreated, this can cause respiratory paralysis, ventricular arrhythmia, and death.
• Medication Errors: Patients must never share their Xultophy pen with others, even if the needle is changed, due to the risk of transmitting bloodborne pathogens.

Pregnancy

It is not known if Xultophy will harm an unborn baby, as there are no adequate and well-controlled studies in pregnant women. Research involving liraglutide, one of the active ingredients in Xultophy, has shown evidence of fetal harm in animal studies, including reduced growth and physical abnormalities. However, animal studies for the other ingredient, insulin degludec, did not show adverse effects on fetal development.

Poorly controlled diabetes during pregnancy increases the risk of complications for both the mother and the fetus, such as birth defects, pregnancy-induced high blood pressure, and stillbirth. If you are pregnant or planning to become pregnant, talk to your healthcare provider about the best way to manage your blood sugar levels.

Breastfeeding

It is unknown whether Xultophy passes into human breast milk or if it has any effect on a nursing infant or milk production. In animal studies, both insulin degludec and liraglutide were found in the milk of lactating rats. Because the risks to a human infant are not established, you should consult with your doctor to determine if you should continue using this medication while breastfeeding.

Available Forms

Xultophy is supplied as a clear, colorless solution for subcutaneous injection. It is available in the following format:

• Pre-filled Pen: A disposable, multi-dose delivery device designed for use by an individual patient.

The medication is administered by injection into the fatty layer under the skin of the thigh, upper arm, or abdomen.

FDA Approval and Indications

Xultophy was approved by the U.S. Food and Drug Administration (FDA) in November 2016. It is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Boxed Warning

The medication carries a boxed warning because one of its active ingredients, liraglutide, has been shown to cause thyroid C-cell tumors in animal studies. It is unknown whether it causes these tumors in humans. Patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) should not use this medication.

Safety Monitoring

The FDA has monitored potential safety signals associated with Xultophy through the FDA Adverse Event Reporting System (FAERS):

• Medication Errors: In early 2018, the FDA identified potential signals related to medication errors, including receiving the wrong drug or dose.
• Gastrointestinal Issues: In 2020, the FDA evaluated reports of ileus (a condition where the muscles of the intestines do not allow food to pass through, resulting in a blockage) associated with GLP-1 receptor agonists like the liraglutide component in Xultophy.

Insurance and Medicare Coverage

Most commercial insurance plans and many Medicare Part D plans provide coverage for Xultophy. However, because it is a brand-name combination drug, it is often placed on a higher formulary tier, which can lead to higher copayments. Some plans may also require prior authorization from a healthcare provider before they will cover the medication.

Manufacturer Assistance

The manufacturer of Xultophy may offer financial assistance to help reduce costs for eligible patients. This often includes savings cards for those with commercial insurance or patient assistance programs for individuals who meet specific income requirements and lack adequate insurance coverage.

Generic Availability

There is currently no generic version of Xultophy available in the United States. Brand-name medications typically maintain higher prices until their patent protections expire and the FDA approves generic alternatives.

Pharmacy Pricing

The retail price of Xultophy can vary significantly between different pharmacies. Patients may find different prices at local retail pharmacies compared to mail-order services or large warehouse clubs.