Liraglutide (Victoza)

Adjunct to diet and exercise to improve glycemic control in type 2 diabetes.

A glucagon-like-peptide (GLP-1) receptor agonist.

Trade name is Victoza.

Trade name for weight loss Saxenda.

A long-acting glucagon-like peptide-1 agonist (GLP-1 agonist) for the treatment of type 2 diabetes.

It reduces meal-related hyperglycemia for 24 hours, by increasing insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.

An acylated human glucagon-like peptide-1 (GLP-1) agonist, with a 97% amino acid sequence identical to endogenous human GLP-1.

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.

Increases intracellular cyclic AMP (cAMP), leading to insulin release in the presence of elevated glucose concentrations.

Insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia.

Also decreases glucagon secretion in a glucose-dependent manner.

It lowers blood glucose in addition, by delaying in gastric emptying.

GLP-1 has a half-life of 1.5–2 minutes by rapid degradation by 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, allowing once daily administration.

It acts in a glucose-dependent manner, stimulating insulin secretion only when blood glucose levels are higher than normal.

Has a negligible risk of hypoglycemia.

It has the potential for stimulating regeneration of beta cells.

In the LEADER study, Liraglutide (Victoza) significantly reduced the risk of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke by 13%.

It decreases appetite, maintains body weight, and lowers blood triglyceride levels.

A once-daily GLP-1 derivative for the treatment of type 2 diabetes.

Has a half-life after subcutaneous injection of 11–15 hours, making it suitable for once-daily dosing.

Byetta form of exenatide, is administered twice daily.

Bydureon form of exenatide is a once weekly form of drug.

The prolonged action of liraglutide is achieved by enabling it to bind to albumin within the subcutaneous tissue and bloodstream, with its release from albumin at a slow, consistent rate.

Binding with albumin results in slower degradation and reduced elimination of from the circulation by the kidneys compared to GLP-1.

Rate of thyroid tumors in patients treated with liraglutide was 1.3 per 1000 patient years compared to 1.0 per 1000 patients in comparison groups.

Serum calcitonin, a biomarker of medulliary thyroid cancer, is slightly increased in liraglutide patients, but still within normal ranges, and it requires ongoing monitoring for 15 years.

No compelling evidence for an increased risk of pancreatitis or pancreatic cancer.

Once daily subcutaneous agent for type 2 diabetes.

Usual Adult Dose for Diabetes Type 2:

Initial dose: 0.6 mg subcutaneously once a day for 1 week; this dose is intended to reduce gastrointestinal symptoms and is not an effective dose for glycemic control.

Maintenance dose: Inject 1.2 mg subcutaneously once a day; if acceptable glycemic control is not achieved, may increase to 1.8 mg subcutaneously once a day

Maximum dose: 1.8 mg once a day

Use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Usual Adult Dose for Weight Loss:

Dose escalation should be followed to reduce the likelihood of gastrointestinal symptoms; dose escalation may be delayed by 1 additional week if necessary:

Week 1: Inject 0.6 mg subcutaneously once a day

Week 2: Inject 1.2 mg subcutaneously once a day

Week 3: Inject 1.8 mg subcutaneously once a day

Week 4: Inject 2.4 mg subcutaneously once a day

Week 5: Inject 3 mg subcutaneously once a day

Maintenance dose: 3 mg subcutaneously once a day

Reduces mean glycated hemoglobin concentration of 0.8 to 1.4 percentage points as compared to placebo.

When compared as monotherapy with a sulfonylurea, this agent was associated with a lower risk of hypoglycemia.

This drug was associated with a greater weight loss then achieved with some active controls.

No need to adjust the dose for patients with renal impairment.

In animal studies associated with C cell hyperplasia, and consideration for medullary thyroid cancer is a concern.

Not first-line therapy for individuals who have inadequate glycemic control to diet and exercise.

Causes dose dependent and treatment related dependent thyroid C cell tumors in rats and mice.

Contraindicated in patients with a family history of medullary carcinoma of the thyroid or in individuals with type 2 multiple endocrine neoplasia syndrome.

May be associated with an increased risk of pancreatitis, and should be used with caution in patients with a histroy of pancreatitis.

Can cause weight loss.

Causes weight loss by reducing appetite and reduces energy intake rather than by increasing energy expenditure.

Adverse reactions include headaches, nausea, diarrhea, and urticaria, diarrhea, constipation, vomiting, hypoglycemia, headache, decreased appetite, and dyspepsia

Acute pancreatitis, cholelithiasis, kidney failure, increased heart rate, suicidal ideation, and neuropsychiatric reactions have been reported in clinical trials.

3 mg daily subcutaneous as an adjunct to diet and exercise is associated with reduced weight and improved metabolic control (Pi-Sunyer et al).

Approved at higher dose as Saxanda for chronic weight management in adults

with BMI greater or equal to 30 for a BMI greater or equal to 27 with weight related comorbidity such as hypertension, dyslipidemia, or diabetes.

Liraglutide is safe, well tolerated and leads to histological resolution of nonalcoholic steatohepatitis.

Decreases caloric intake, possibly due to delayed gastric emptying and agonist effects on GLP-1 receptors in areas of the brain involved in appetite regulation.

Added to high dose insulin therapy improves glycemic control, decreases bodyweight, enhances treatment satisfaction in difficult to treat patients with high dose insulin requirements (Vanderheiden A et al).

Mechanism of action for weight loss is that decreases caloric intake.

Delays gastric emptying and has agonist effect on GLP-1 receptor areas of the brain are involved in appetite regulation have been implicated.

In obese adolescents its use plus lifestyle therapy lead to significant greater reductions in BMI than placebo plus lifestyle therapy. (Kelly AS).

Combining exercise and liraglutide therapy improves healthy weight loss maintenance more than either treatment alone.


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