Antidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist; Insulin, Long-Acting
“ALERT: US Boxed Warning
Thyroid C-cell tumor risk:
Liraglutide, one of the components of insulin degludec/liraglutide, causes dose-dependent and treatment duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether insulin degludec/liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
Insulin degludec/liraglutide is contraindicated in patients with a personal or family history of MTC and in patients with multiple endocrine neoplasia syndrome types 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of insulin degludec/liraglutide and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with insulin degludec/liraglutide.”
CSA NA – FDA Approved – REMS (N) – Can Ship
How Does It Work
Liraglutide is a long-acting analog of human glucagon-like peptide-1 (GLP-1) (an incretin hormone). Liraglutide works in multiple of ways to lower blood glucose and hemoglobin A1C. Liraglutide stimulates the beta cells of the pancreas to release insulin when blood glucose levels are high. Liraglutide slows down gastric emptying and the rate at which glucose enters the blood after meals. Liraglutide also helps lower hepatic glucose output by suppressing pancreatic glucagon secretion.
Insulin degludec, Tresiba works on the liver, muscle, and adipose (fat) tissue to regulate the metabolism of carbohydrates, protein, and fats. In the liver and muscles, it increases glycogen synthesis which is the immediate storage form of glucose. It increases fat production by increasing fatty acid release from the liver in the form of lipoproteins which adipose tissue converts to fatty acids than to triglycerides for storage whilst also stopping the metabolism of triglycerides (fat). Insulin also increases the cellular uptake of amino acids and some electrolytes such as potassium into the cell. In muscle tissue, protein synthesis is increased.
Normally insulin is produced by the pancreas however insulin products for pharmaceutical use have been produced via recombinant DNA technology using certain bacteria (they splice the gene for insulin production into bacterial DNA so the cell produces insulin – a gene is a portion of DNA or RNA that produces one specific protein). Insulin degludec is different from human insulin as it has some modifications to make it last longer. It involves the omission of the amino acid threonine in position B-30 of the B-chain, and the subsequent addition of a side chain composed of glutamic acid and a C16 fatty acid for a glycine (these are all names of amino acids which are the building blocks of proteins such as insulin).
Indications For Use
Officially indicated for the treatment of Diabetes mellitus type 2.
Before starting Liraglutide+Insulin Degludec, Xultophy makes sure your physician is aware of any allergies or medications you currently take if you have had bariatric surgery, cardiovascular disease, have kidney disease, liver disease, diabetic ketoacidosis, are pregnant or breastfeeding. Liraglutide+Insulin Degludec, Xultophy use has been associated with rare but serious adverse events such as antibody formation, gallbladder disease, GI symptoms, hyper/hypoglycemia, hypersensitivity, hypokalemia, pancreatitis, renal effects, and thyroid tumor.
Patients naive to basal insulin or a GLP-1 agonist: 10 units (insulin degludec 10 units/liraglutide 0.36 mg) once daily.
Patients currently on basal insulin or a GLP-1 agonist: 16 units (insulin degludec 16 units/liraglutide 0.58 mg) once daily.
Note: Discontinue therapy with basal insulin or a GLP-1 agonist prior to initiation of the combination product.
Dose titration: Titrate dosage upwards or downwards by 2 units (insulin degludec 2 units/liraglutide 0.072 mg) once or twice weekly (every 3 to 4 days) until the desired fasting plasma glucose is achieved. Maximum dose: 50 units (insulin degludec 50 units/liraglutide 1.8 mg)/day
Missed dose: Resume with the next regularly scheduled dose; do not administer an extra dose or increase dose to account for a missed dose. If more than 3 days have elapsed since the last dose, reinitiate at the initial dosage once daily
Pharmacist Tips On Using
How to Use: For subcutaneous use only. Inject into the abdomen, thigh, or upper arm. Rotate injection sites for each dose. Administer once daily at the same time each day with or without food. The solution should appear clear and colorless. Prefilled pen dials in 1-unit increments. Prior to initial use, store pens at 2°C to 8°C (36°F to 46°F). Protect from light. After initial use, may store for up to 21 days at room temperature (15ºC to 30°C [59ºF to 86°F]) or under refrigeration (2ºC to 8ºC [36ºF to 46ºF]). Replace the pen cap after each use.
You Need to Avoid: Do not administer IM, IV, or via an insulin pump. Cold injections should be avoided; do not use the same site for each injection to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase the risk of hypoglycemia. Do not split the dose use once daily. Do not use if particulate matter or coloration is seen. Do not mix or dilute with any other insulin or solution. Do not freeze (discard if frozen). Do not store with a needle attached.
Well tolerated, most side effects are transient and mild to moderate in nature. The most common side effects include tachycardia, headache, hypoglycemia, nausea, diarrhea, constipation, vomiting, injection site reaction, antibody development, nasopharyngitis, upper respiratory tract infection.
Frequently Asked Questions
What is hypoglycemia?
Hypoglycemia is a condition of low blood sugar (>3.9mmol/L-Canada; 70mg/dL-US) which is considered a medical emergency whereas hyperglycemia is a slowly progressive condition. It generally occurs with irregularities in diet, exercise, and medications in diabetic patients. It is preferably treated with simple sugars such as dextrose; regular table sugar can work but is slower acting as it needs to be digested and if blood sugar is extremely low this delay can be a problem. Hypoglycemia has a large host of progressive symptoms from hunger, headache, nausea, sweating, palpitations, mood swings, irritability to seizure, coma and in severe cases, death.