Insulin degludec and Liraglutide

XULTOPHY 100/3.6 is a combination of insulin degludec and liraglutide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: • XULTOPHY 100/3.6 contains liraglutide. Coadministration with any other product containing liraglutide or another glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended. • XULTOPHY 100/3.6 is not recommended for the treatment of diabetic ketoacidosis. • XULTOPHY 100/3.6 has not been studied in combination with prandial insulin. XULTOPHY 100/3.6 is a combination of insulin degludec, a long-acting human insulin analog, and liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

XULTOPHY 100/3.6 XULTOPHY 100/3.6 is a combination product consisting of insulin degludec and liraglutide. Insulin degludec The primary activity of insulin degludec is the regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis. Liraglutide Liraglutide is a GLP-1 receptor agonist that increases glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying.

• Administer once-daily at same time each day with or without food. • XULTOPHY 100/3.6 pen delivers doses from 10 to 50 units with each injection, each XULTOPHY 100/3.6 dosage unit contains 1 unit of insulin degludec and 0.036 mg of liraglutide. • Maximum daily dosage is 50 units (50 units of insulin degludec and 1.8 mg of liraglutide). • Recommended starting dosage in patients naïve to basal insulin or GLP-1 receptor agonist is 10 units (10 units of insulin degludec and 0.36 mg of liraglutide) injected subcutaneously once-daily. • Discontinue therapy with liraglutide or basal insulin prior to initiation of XULTOPHY 100/3.6. • Recommended starting dosage in patients currently on basal insulin or GLP-1 receptor agonist is 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) injected subcutaneously once-daily. • See Full Prescribing Information for titration recommendations.

XULTOPHY 100/3.6 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). • During episodes of hypoglycemia. • In patients with hypersensitivity to insulin degludec, liraglutide, or any of the excipients in XULTOPHY 100/3.6. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide, one of the components of XULTOPHY 100/3.6. • Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2. • During episodes of hypoglycemia.

Boxed warning (risk of thyroid c-cell tumors •): Liraglutide, one of the components of XULTOPHY 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. • Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including liraglutide. Discontinue if pancreatitis is suspected. • Never share a XULTOPHY 100/3.6 pen between patients, even if the needle is changed. • Hyperglycemia or hypoglycemia with changes in insulin regimen: Make changes to a patient’s insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. • Overdose due to medication errors: XULTOPHY 100/3.6 contains two drugs.

The following serious adverse reactions are described below or elsewhere in the prescribing information: • Risk of Thyroid C-cell Tumors • Acute Pancreatitis • Hypoglycemia • Acute Kidney Injury Due to Volume Depletion • Severe Gastrointestinal Adverse Reactions • Hypersensitivity Reactions • Acute Gallbladder Disease • Hypokalemia • Pulmonary Aspiration During General Anesthesia or Deep Sedation • Most common adverse reactions (incidence ≥5%) in clinical trials are nasopharyngitis, headache, nausea, diarrhea, increased lipase and upper respiratory tract infection. • Immunogenicity-related events, including urticaria, were more common among liraglutide-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials.

• Drugs that affect glucose metabolism: Adjustment of XULTOPHY 100/3.6 dosage may be needed, closely monitor blood glucose. • Anti-Adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Hypoglycemia signs and symptoms may be reduced or absent. • Effects of delayed gastric emptying on oral medications: May impact absorption of concomitantly administered oral medications.

Prior to first use, XULTOPHY 100/3.6 should be stored between 36°F to 46°F (2°C and 8°C) until the expiration date printed on the label. Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze. After first use, the XULTOPHY 100/3.6 pen can be stored for 21 days at controlled room temperature 59°F to 86°F (15°C to 30°C) or in a refrigerator 36°F to 46°F (2°C to 8°C).