Victoza® (liraglutide) injection
Victoza
Liraglutide
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About Victoza

Victoza (liraglutide) is considered an injectable incretin mimetic, that is a relatively new drug used for the treatment of type 2 diabetes.

It is commonly recommended for adults and children over the age of 10 with type 2 diabetes to be used in conjunction with diet and lifestyle modifications in order to improve glycaemic control.

Incretin mimetics have been proven to be effective in lowering blood glucose and through clinical research studies, they have also shown to be beneficial for weight loss when compared to subjects on the placebo, when used in combination with diet and exercise.

The FDA first approved Victoza for medical use in adults with type 2 diabetes in 2010 followed by approval in 2019 for the use in children older than 10 years with type 2 diabetes. It has become the only non-insulin drug approved by the FDA to be used in the paediatric population since metformin was approved for pediatric use in 2000.

The FDA has issued a black box warning with regards to the increased risk of thyroid tumours with the use of Victoza. During the animal trials, it has been shown that Victoza has caused certain cancers in animals. The most frequently noted cancer was medullary thyroid carcinoma (MTC) which is a cancer that arises from the C cells of the thyroid gland. Even though it is reported in animal trials, the effect of Victoza on thyroid tumours in humans is not known. But as a safety precaution, it is avoided in patients with a past history or family history of MTC. Patients who receive Victoza treatment are monitored closely for possible signs and symptoms of MTC. The most common signs and symptoms of MTC are the presentations of a neck lump, dysphagia (which is having trouble swallowing), hoarseness of voice and shortness of breath. It is important to withhold treatment if these signs arise. The doctor and patient both should be alert for possible warning signs.

How is blood glucose levels regulated in our body?

Glucose is the body’s primary source of energy and in fact the obligatory source of energy for the adult brain; cells use glucose and fatty acids along with amino acids for cellular metabolism. The need to maintain adequate fuel supplies in the face of intermittent food intake and variable metabolic demands is fulfilled by careful balance between the 2 main glucose regulating hormones; insulin and glucagon. Insulin is the main hormone controlling intermediary metabolism, having its main actions on liver, fat and muscle. It is an anabolic hormone: its overall effect is to conserve fuel by facilitating the uptake and storage of glucose, amino acids and fats after a meal. Its most striking acute effect is to lower blood glucose. When we eat in excess, the excessive calories are stored as glycogen in the liver and muscle or fat in adipose tissue. During fasting, these energy stores need to be mobilized in a regulated manner.

Insulin is secreted by ? cells located in the Islets of Langerhans in the pancreas. Many factors stimulate insulin secretion, but the main one is blood glucose. Incretins, especially GIP and GLP-1 secreted, respectively, by K and L cells in the gut are also important.

Insulin has essential metabolic actions as a fuel storage hormone and also affects cell growth and differentiation. It decreases blood glucose by:

  • Increasing glucose uptake into muscle and fat / adipose tissue via Glut-4
  • Increasing glycogen synthesis
  • Decreasing gluconeogenesis
  • Decreasing glycogen breakdown.

What is Diabetes?

Diabetes mellitus is a chronic metabolic disorder in which persistent hyperglycaemia is caused by deficient insulin secretion or by resistance to the action of insulin. This leads to the abnormalities of carbohydrate, fat and protein metabolism that are characteristic of diabetes.

Hyperglycaemia occurs as a result of uncontrolled glucose output from the liver and reduced uptake of glucose by skeletal muscle with reduced glycogen synthesis. Insulin deficiency causes muscle wasting through increased breakdown and reduced synthesis of proteins.

An estimated 25.8 million people in the United States and 347 million people worldwide are afflicted with diabetes. Type 1 and type 2 diabetes are the two most common classifications of diabetes.

Type 1 diabetes is characterized by an absolute deficiency of insulin due to destruction of cells by an autoimmune-mediated processes that may be triggered by viruses or other environmental toxins.

Type 2 diabetes is a chronic metabolic condition characterized by insulin resistance (lack of sensitivity of target organs to insulin) followed by ?-cell dysfunction and insufficient insulin production, which leads to hyperglycemia.

Aims of treatment

Treatment is aimed at minimizing the risk of long-term microvascular and macrovascular complications by effective blood-glucose control and maintenance of HbA1c at or below the target value set for each individual patient. Specialized diet and lifestyle advice is of paramount importance in managing diabetes. Weight loss, smoking cessation and regular exercise can help to reduce hyperglycaemia and reduce cardiovascular risk. Antidiabetic drugs should be prescribed to augment lifestyle interventions, when these changes are not adequate to control blood glucose alone.

Antidiabetic drugs

There are several classes of non-insulin antidiabetic drugs available for the treatment of type 2 diabetes. The choice of drug should be based on effectiveness, safety, tolerability and should also take into consideration the patient’s comorbidities and concomitant medication. Oral antidiabetes drugs are either,

  • Secretagogue therapy to increase endogenous insulin release (Sulphonyureas, Incretin mimetics like Victoza)
  • Insulin sensitisers to reduce insulin resistance, or (Eg. Metformin)
  • Drugs aimed at modifying absorption of glucose.

Role of incretins in regulating blood glucose

Incretins play a major role in regulating insulin secretion after a meal. When a meal is taken, our gut secretes a set of hormones called incretins, namely glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide which stimulate secretion of insulin from the pancreas and responsible for 60% to 70% of postprandial insulin secretion. Therefore, oral glucose results in a higher secretion of insulin than occurs when an equal load of glucose is given IV. This effect is referred to as the “incretin effect” and is markedly reduced in type 2 diabetes. Victoza / Liraglutide is an injectable incretin mimetic used for the treatment of type 2 diabetes.

Mechanism of action of Victoza

Victoza / Liraglutide is a functional analogue of the incretin hormone glucagon-like peptide-1 (GLP-1), an incretin analogues / mimetic. Aside from boosting insulin secretion, they have other actions which offer potential advantages over other insulin secretagogues in diabetes:

  • Reducing post-prandial glucagon secretion
  • Slowing gastric emptying
  • Reducing food intake by enhancing satiety (a feeling of fullness) by way of acting on GLP-1 receptors in the brain
  • Increase ?-cell mass
    • Animal studies suggest that there may be a stimulatory effect of GLP-1 analogues on beta cell mass although this has not yet been demonstrated reliably in humans.

Consequently, weight gain and postprandial hyperglycaemia are reduced, and HbA1c levels decline. It also has proven to reduce the incidence of cardiovascular events such as stroke and heart diseases

Pharmacokinetics of the drug

Being a polypeptide, Victoza / liraglutide must be administered subcutaneously. Liraglutide is highly protein bound and has a long half-life, allowing for once-daily dosing without regard to meals.

Indications

GLP-1 therapy is currently aimed at overweight patients with type 2 diabetes where sulfonylureas or insulin therapy may promote weight gain. Therefore, liraglutide should only be prescribed for patients who have a,

  • BMI of 35 kg/m2 or above (adjusted for ethnicity) and who also have specific psychological or medical problems associated with obesity
  • BMI lower than 35 kg/m2 but for whom insulin therapy would have significant occupational implications
  • If the weight loss associated with Victoza would benefit other significant obesity-related comorbidities.

After 6 months, the drug should be reviewed and only continued if there has been a beneficial metabolic response (a reduction of at least 11 mmol/mol [1.0 %] in HbA1c and a weight loss of at least 3% of initial body-weight).

Dose and administration

Liraglutide is administered as a subcutaneous injection, initially 0.6 mg once daily for at least 1 week, then increased to 1.2 mg once daily for at least 1 week, then increased if necessary to 1.8 mg once daily twice or once daily. Dose of concomitant insulin or sulfonylurea may need to be reduced if these drugs are administered together.

A Victoza pen contains 18mg of liraglutide in 3mL of solution and the pen pen delivers three ranges of doses (0.6 mg, 1.2 mg and 1.8mg).

Side effects

Victoza can cause mild or serious side effects. The following list depicts subset of side effects that you will experience while taking Victoza. However, this does not contain all possible side effects. Talk with your doctor or pharmacist for more information on the potential side effects of Victoza.

Common side effects

  • Nausea (the most common side effect)
  • Vomiting
  • Constipation
  • Diarrhoea
  • Dizziness
  • Dry mouth
  • Gallbladder disorders (cholelithiasis or cholecystitis)
  • Gastrointestinal discomfort
  • Gastrointestinal disorders
  • Insomnia
  • Taste altered

Uncommon side effects

  • Malaise
  • Pancreatitis (Inflammation of the pancreas)
    • Patients should be advised to discontinue and immediately contact their health care provider if symptoms of acute pancreatitis occur, such as persistent, severe abdominal pain.
  • Tachycardia
  • Urticaria

Rare side effects

  • Renal impairment ( Functional impairment of kidneys)
    • Due to dehydration resulting from gastro-intestinal side-effects.
    • Therefore, should take precautions to avoid fluid depletion

However, these side effects tend to resolve within a few days / weeks, depending on the time taken by the body to adapt to the drug. If common side effects do not improve by over a few weeks, a dose adjustment by a qualified physician might be necessary.

Liraglutide causes thyroid C-cell tumours in rodents. However, it is unknown if it causes these tumours or thyroid carcinoma in humans.

Contraindications

  • Past history or family history of Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplastic Syndrome type 2 (MEN 2)
  • History of the prior event of serious hypersensitivity reaction to liraglutide or any of the excipients in Victoza
  • Diabetic gastroparesis
  • Inflammatory bowel disease
  • Diabetic ketoacidosis

Cautions: Thyroid disease

Do not take Victoza if you are

  • Pregnant
    • Should be avoided during pregnancy
    • Toxicity has been showed in animal studies
  • Breast feeding
    • Should be avoided in breast feeding
    • Animal studies suggest that transfer into breast milk is low, but the extent of excretion into human milk is not known
    • If given, blood glucose monitoring of the infant should be considered
  • Hepatic impairment
    • Should be avoided in severe liver impairment.

Handling and Storage

Victoza should be stored in a refrigerator (2–8°C). It can also be stored below 30°C after first use and should be used within 1 month. The cap on the pen should be kept in place to protect from light.

Advice for patients and caregivers

  • The solution should be observed before a