Liraglutide

Liraglutide is indicated: • as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus, • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease. Limitations of Use: Liraglutide contains liraglutide. Coadministration with other liraglutide-containing products is not recommended. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated: • as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. • to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease.

Liraglutide is an acylated human GLP-1 receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1. Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Liraglutide increases intracellular cyclic AMP (cAMP) leading to insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner. The mechanism of blood glucose lowering also involves a delay in gastric emptying.

• Adult Patients: Initiate at 0.6 mg injected subcutaneously once daily for one week then increase to 1.2 mg daily. If additional glycemic control is required, increase the dose to 1.8 mg daily after one week of treatment with the 1.2 mg daily dose. • Pediatric Patients: Initiate at 0.6 mg injected subcutaneously once daily for at least one week. If additional glycemic control is required increase the dose to 1.2 mg daily and if additional glycemic control is still required, increase the dose to 1.8 mg daily after at least one week of treatment with the 1.2 mg daily dose. • Inspect visually prior to each injection. Only use if solution is clear, colorless, and contains no particles. • Inject liraglutide subcutaneously once-daily at any time of day, independently of meals, in the abdomen, thigh or upper arm. • When using liraglutide with insulin, administer as separate injections.

Liraglutide 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). • serious hypersensitivity reaction to liraglutide or to any of the excipients in liraglutide. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide. • Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2. • Patients with a serious hypersensitivity reaction to liraglutide or any of the excipients in liraglutide.

Boxed warning (risk of thyroid c-cell tumors •): 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 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. • Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including liraglutide. Discontinue if pancreatitis is suspected. • Never Share a Liraglutide Pen Between Patients, even if the needle is changed. • Hypoglycemia: Adult patients taking an insulin secretagogue or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.

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 • Pulmonary Aspiration During General Anesthesia or Deep Sedation • Most common adverse reactions (incidence ≥5%) in clinical trials are nausea, diarrhea, vomiting, decreased appetite, dyspepsia, constipation. • Immunogenicity-related events, including urticaria, were more common among liraglutide-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials.

Effects of delayed gastric emptying on oral medications: Liraglutide delays gastric emptying and may impact absorption of concomitantly administered oral medications.

Storage Prior to first use, liraglutide injection should be stored in a refrigerator between 36°F to 46°F (2°C to 8°C). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze liraglutide injection and do not use liraglutide injection if it has been frozen. After first use of the liraglutide injection pen, the pen can be stored for 30 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). Always remove and safely discard the needle after each injection and store the liraglutide injection pen without an injection needle attached.