Liraglutide

Liraglutide is an acylated human Glucagon-Like Peptide-1 (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.

GLP-1(7-37) has a half-life of 1.5-2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once daily administration, is a result of self-association that delays absorption, plasma protein binding and stability against metabolic degradation by DPP-IV and NEP.

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. Never mix.

Effects of Delayed Gastric Emptying on Oral Medications: Liraglutide causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, Liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Nonetheless, caution should be exercised when oral medications are concomitantly administered with Liraglutide.

Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin: Liraglutide stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving Liraglutide in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. When initiating Liraglutide, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia.

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

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.

Liraglutide is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. There are no available data with liraglutide in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Liraglutide should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Liraglutide should be discontinued.

There are no data on the presence of liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. Liraglutide was present in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Liraglutide and any potential adverse effects on the breastfed infant from Liraglutide or from the underlying maternal condition.

Pancreatitis: Postmarketing reports, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. Discontinue promptly if pancreatitis is suspected. Do not restart if pancreatitis is confirmed. 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. In pediatric patients 10 years of age and older, the risk of hypoglycemia was higher with Liraglutide regardless of insulin and/or metformin use. Reduction in the dose of insulin secretagogues or insulin may be necessary.

Acute Kidney Injury: Postmarketing, usually in association with nausea, vomiting, diarrhea, or dehydration which may sometimes require hemodialysis. Use caution when initiating or escalating doses of VICTOZA® in patients with renal impairment.

Hypersensitivity Reactions: Postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema). Discontinue Liraglutide and promptly seek medical advice.

Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated.

Pulmonary Aspiration During General Anesthesia or Deep Sedation: Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures.

Overdoses have been reported in clinical trials and post-marketing use of liraglutide. Effects have included severe nausea, severe vomiting and severe hypoglycemia. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.

GLP-1 receptor agonists

Store between 2-8°C. Do not freeze. After initial use, it can be stored between 15-30°C for 30 days. Protect from heat and light.