Mechanism of Action

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. 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 is a Glucagon-Like Peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin release, decreases glucagon secretion and slows gastric emptying.

Side Effects

Adverse events associated with the use of Xultophy 100/3.6 may include, but are not limited to, the following:

Nasopharyngitis

Headache

Nausea

Diarrhea

Increased lipase

Upper respiratory tract infection

Xultophy 100/3.6 comes with the following black box warning:

Liraglutide, one of the components of Xultophy 100/3.6, causes thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Xultophy 100/3.6 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. Xultophy 100/3.6 is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).

Dosing/Administration

Xultophy 100/3.6 is supplied as an injection for subcutaneous administration in thigh, upper arm or abdomen. Prior to administration with Xultophy 100/3.6, the use of liraglutide or basal insulin should be discontinued. The recommended starting dosage is 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) given subcutaneously once daily. Xultophy 100/3.6 should be administered once daily at the same time each day with or without food. The maximum daily dosage is 50 units (50 units of insulin degludec and 1.8 mg of liraglutide). 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. Alternative antidiabetic products should be used if patients require a Xultophy 100/3.6 daily dosage: persistently below 16 units or over 50 units. Please see full prescribing information for titration recommendations.

Clinical Trial Results

FDA Approval

The FDA approval of Xultophy 100/3.6 was based on efficacy and safety data from the DUAL (Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) clinical development program. In three DUAL trials involving 1,393 adults with type 2 diabetes, patients who were inadequately controlled on liraglutide or basal insulin therapy and switched to Xultophy 100/3.6 achieved reductions in A1C. For adults uncontrolled on basal insulin, Xultophy 100/3.6 demonstrated significant reductions in A1C from baseline of 1.67 percent and 1.94 percent.