Liraglutide

Indications

Liraglutide is used for: Type 2 diabetes

Adult Dose

Subcutaneous Adjunct to Type 2 diabetes mellitus Adult: Initially, 0.6 mg/day may increase to 1.2 mg/day after 1 wk; and a further increase to 1.8 mg/day after 1 wk if glycaemic control is not optimal. Initial dose of 0.6 mg SC qDay is only to decrease GI adverse effects and does not provide glycemic control. When initiating , consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycemia Hepatic Impairment: No dosage adjustment needed.

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal Impairment No dosage adjustment needed.

Administration

It can be administered once daily at any time of day, independently of meals, and can be injected subcutaneously in the abdomen, thigh or upper arm. The injection site and timing can be changed without dose adjustment. If dose missed, resume the once-daily regimen with the next scheduled dose; do not give an extra dose or a higher dose; if missed dose more than 3 days, initiate therapy at 0.6 mg/day to avoid GI symptoms

Contra Indications

Do not use in patients with a prior serious hypersensitivity reaction to any of the product components. Type 1 DM, diabetic ketoacidosis. Severe renal impairment & end-stage renal disease. Pregnancy & lactation. Contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2)

Precautions

CHF, inflammatory bowel disease, diabetic gastroparesis, preexisting thyroid disease. Increased risk of hypoglycaemia w/ sulfonylurea. Hepatic impairment. Do not administer via IV or IM. May affect ability to drive or operate machinery. Childn <18 yr. Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide. Not for use in patients with type 1 diabetes mellitus or for treatment of diabetic ketoacidosis. Resting heart rate may increase by 2 to 3 bpm; up to 10-20 bpm increases also reported. Not a substitute for insulin. Lactation: Unknown if excreted in human milk; either discontinue drug or nursing

Pregnancy-Lactation

Pregnancy Based on animal reproduction studies, there may be risks to the fetus from exposure during pregnancy Use during pregnancy only if the potential benefit justifies the potential risk to the fetus Animal data Animal reproduction studies identified increased adverse developmental outcomes from exposure during pregnancy Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 1.8 mg/day In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD Clinical considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications Poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity Lactation There are no data on the presence of drug in human milk, the effects on the breastfed infant, or the effects on milk production Present in milk of lactating rats

Interactions

Oral Contraceptives: Liraglutide lowered ethinyloestradiol and levonorgestrel Cmax by 12% and 13%, respectively, following administration of a single dose of an oral contraceptive product. Tmax was delayed by 1.5 hrs with liraglutide for both compounds. There was no clinically relevant effect on the overall exposure of either ethinyloestradiol or levonorgestrel. The contraceptive effect is therefore anticipated to be unaffected when co-administered with liraglutide. Increased risk of hypoglycaemia when used w/ insulin secretagogues (e.g. sulfonylurea, meglitinide). May affect absorption of concomitantly administered oral drugs due to slow gastric emptying. Insulin: Combination of Liraglutide with insulin has not been evaluated.

Adverse Effects

Side effects of Liraglutide : >10% Nausea (26%), Diarrhea (17%), Vomiting (11%) 1-10% Constipation (10%), Headache (9%), Antiliraglutide antibodies (7%), Injection-site reactions (2%) <1% (Victoza) Urticaria, Upper respiratory tract infection, UTI, Dizziness, Sinusitis, Nasopharyngitis, Back pain, Hypertension, Hypoglycemia (mostly in combination therapy), Pancreatitis, Papillary thyroid carcinoma, Thyroid C-cell hyperplasia

Mechanism of Action

Incretin mimetic; analogue of human glucagonlike peptide-1 (GLP-1); acts as GLP-1 receptor agonist to increase insulin secretion in the presence of elevated blood glucose; delays gastric emptying to decrease postprandial glucose; also decreases glucagon secretion.