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.
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.
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:
- 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).
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)
- Dry mouth
- Gallbladder disorders (cholelithiasis or cholecystitis)
- Gastrointestinal discomfort
- Gastrointestinal disorders
- Taste altered
Uncommon side effects
- 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.
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.
- 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
- 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 administration to ensure that it is clear, colourless and there are no particles.
- It is injected once daily, independently of meals. A missed dose should never be given closer to the next dose as it can lead to a hypoglycaemic crisis by a sudden drop in blood glucose levels.
- If Victoza and insulin are co-administered, they should be given as separate injections. They should never be mixed.
- The likelihood of hypoglycaemia increases with concomitant use of Victoza with other anti-diabetic drugs, leading to the sudden lowering of blood glucose levels.
Signs and symptoms associated with the hypoglycaemic condition are as follow:
- Fogy vision with light-headedness
- Fluctuations in heartbeat
- Increase in thrust and hunger
- A profound state of confusion
- Increased Sweating
- Do not drive if you face a hypoglycaemic condition or handle projects which require prompt alertness.
- Do not use too much alcohol with the medication course.
- Children (especially those under 10 years of age) are at more risk of hypoglycaemia. Therefore, blood sugar levels should be monitored regularly.
- You should be able to recognise signs and symptoms of acute pancreatitis and should seek immediate medical attention if symptoms develop.
- You should know the potential risk of dehydration in relation to gastro-intestinal side-effects and should take precautions to avoid fluid depletion
- You should be able to recognize the symptoms of cholelithiasis and cholecystitis. Symptoms include:
- Jaundice (which indicates raised bilirubin levels presents as yellowish discolouration of skin and sclera)
- Pain in the right adjacent area of the stomach
- Your healthcare provider will watch for the following signs and symptoms to pick up any neoplastic growth at the earliest as thyroid related cancers are a major concern with the use of Victoza.
- Shortness of breath
- Hoarsening of the voice
- Unexplained and sudden occurrence of lumps / swelling in the neck area
- Swollen lymph nodules on the neck
- Recurrent episodes of fever
- Warmth around the neck
- Victoza is only recommended in pregnancy if the potential benefits outweigh the risks and the decision should be made by your health expert / consultant / physician.
- Pen sharing among individuals is discouraged as blood borne pathogens might transmit from patient to patient.
- Disposal should be done after ensuring the following safety precautions.
- After using the Victoza pen, remove the un-sterile needle
- Discard the used needle carefully after decamping
- Keep the rest of the drug container closed