Victoza is a popular diabetes medication administered once-a-day via injection. While shown to be effective in controlling blood sugar levels, the drug was approved by the U.S. Food and Drug Administration (FDA) with certain contingencies for further evaluation and study to ensure its benefits continue to outweigh any safety risks to patients. One of the safety trials required by the FDA includes a large cardiovascular safety trial that is now required as a part of the development of most diabetic medications.
Other safety concerns raised during Victoza’s development include the drug’s association to potentially life-threatening pancreatitis and a rare form of thyroid cancer called medullary thyroid cancer (MTC), that is sometimes difficult to treat. Postmarketing reports have further confirmed these serious side effects and their link to Victoza-use.
Kidney impairment and/or kidney failure
Hypersensitivity (allergic) reactions, including:
- Anaphylaxis – a serious, potentially deadly allergic reaction affecting the entire body
- Angioedema – swelling underneath the skin
Acute gallbladder disease, such as:
- Cholelithiasis – hardened deposits of digestive fluid that forms in the gallbladder
- Cholecystitis – sudden inflammation of the gallbladder
Victoza and Thyroid Cancer
Liraglutide, the active ingredient in Victoza, has been shown to cause thyroid C-cell tumors, both benign and cancerous, at clinically relevant exposures in both male and female rats and mice. Malignant thyroid C-cell carcinomas, meaning a cancerous tumor able to invade nearby tissues and organs, were detected in rats and in mice in laboratory studies.
Results of the studies showed that liraglutide caused malignant tumors of the thyroid gland, especially when taken at high doses, eight times higher than the recommended human dose, according to safety information regarding Victoza issued by the FDA.
The results of the animal studies prompted blood calcitonin (a hormone produced by the C cells of the thyroid) tests as a part of the clinical development program for Victoza. Data from the two-year study did not show any difference in calcitonin levels between patients treated with Victoza compared to other diabetes medications.
Despite this being enough to satisfy the FDA regarding the safety concern of the risk of thyroid cancer raised during Victoza’s development, it is still unknown whether these same thyroid C-cell tumors that resulted in rodents can occur as a result of Victoza-use in humans. The human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined, according to the drug’s label.
For this reason, the drug’s approval was contingent upon further post-marketing safety evaluation and long-term studies.
Even without using Victoza, only about 600 cases of the specific type of thyroid cancer – medullary thyroid cancer (MTC) – occur in the United States each year. Therefore, the FDA concluded that due to the already rare incidence of the cancer, even if liraglutide did increase a patient’s risk of developing it, cases might not be detected during clinical trials.
However, postmarketing reports have revealed cases of MTC in patients treated with Victoza. The data in these reports are insufficient to establish or exclude a causal link between the incidence of MTC and Victoza-use in humans.
What Is the Thyroid and What Does It Do?
The thyroid is an endocrine gland shaped like a butterfly that is located in the lower front of the neck, just above the collarbone. Endocrine glands secrete the hormones they produce directly into the blood rather than through a duct.
The thyroid is responsible for making and releasing thyroid hormones (T3 and T4), or tyrosine-based hormones (one of 20 essential amino acids used by cells to synthesize – make by a chemical process – proteins). These hormones help the body work properly.
Thyroid hormones are produced through the use of iodine from foods we eat. The hormones are carried by the blood to the tissues in the body, where they are primarily responsible for the regulation of metabolism. Metabolism is the set of life-sustaining chemical transformations that take place within a living organism’s cells.
- Converting food (fuel) to energy for cellular processes
- Converting food (fuel) to building blocks for proteins, lipids, nucleic acids and some carbohydrates
- Elimination of nitrogenous wastes (ammonia, urea or uric acid)
- Helping the body to use energy efficiently
- Keeping the body warm, or regulating body temperature
- Keeping the brain, heart, muscles and other organs working properly
- Helping to regulate long bone growth and nervous system development
- Regulating protein, fat and carbohydrate metabolism
- Controlling a person’s metabolism rate, or how fast or how slow different parts of the body work
When the thyroid isn’t working properly and has person has too little thyroid hormone, they may feel tired, cold or gain weight. Contrarily, when a person has too much thyroid hormone, they may feel anxious, restless, warm or lose weight.
Development of Medullary Thyroid Cancer (MTC)
Thyroid cancer is rare compared to other types of cancer in the U.S. In 2016, approximately 64,000 people were diagnosed with thyroid cancer, while a significantly higher number of patients totaling 240,000 were diagnosed with breast cancer.
Medullary thyroid cancer (MTC) is even more uncommon, accounting for only about four percent of all thyroid cancers in the United States, according to the American Cancer Society.
Unlike other thyroid cancers derived from thyroid follicular cells (or the cells that make thyroid hormone), MTC starts in cells in the thyroid gland called parafollicular C cells, or just C cells. These cells release a hormone called calcitonin. This hormone controls the amount of calcium and phosphate in the blood and promotes bone formation.
MTC often spreads to nearby lymph nodes and other organs, such as the lungs or liver. The exact cause of MTC is unknown, but it can be acquired sporadically or genetically. The sporadic form is most common, occurring in about 75 percent of patients with MTC and primarily affecting adults.
A blood test for gene mutation in the RET protooncogene, present in all the cells in the body (a germline mutation), can pinpoint whether MTC is familial (inherited) or sporadic.
Signs and Symptoms of Medullary Thyroid Cancer (MTC)
Medullary thyroid cancer (MTC) begins as a small lump, or nodule, in the thyroid gland. The patient may notice the lump on their own or it may be found by a doctor during a routine physical examination.
Sometimes, patients might not present with any other symptoms, especially in the beginning stages of the cancer. In other cases, when the cancer has already spread to the lymph nodes in the neck, the patient may experience swelling in the neck where the nodes are located.
MTC is usually the most aggressive form of thyroid cancer. In its advanced stages, symptoms of MTC may include pain in the neck, jaw or ear. If the nodule in the thyroid is large, it can press against the esophagus, causing the airways to narrow and resulting in difficulty breathing and/or swallowing.
- Hoarseness, when the cancer affects the vocal cords
- Cough with blood
- Diarrhea due to high calcitonin level
A type of thyroid function test called a thyroid-stimulating hormone (TSH) blood test is used to check for problems with the thyroid gland. However, this test may be normal in patients with MTC.
Treatment of Medullary Thyroid Cancer (MTC) and Patient Outlook
Medullary thyroid cancer is difficult to find and treat. However, once diagnosed, surgery is typically the first line of treatment to remove the thyroid and surrounding lymph nodes . Because this type of tumor is uncommon, the related surgery should be performed by a surgeon who is familiar with the cancer and experienced with MTC removal. Patients who undergo surgery to remove the cancerous gland will have to take medicine for the rest of their lives to replace hormones made by the thyroid.
Chemotherapy and radiation, two types of treatment often used in other types of cancer to prolong patients’ lives, reduce symptoms, kill cancer cells and help prevent the cancer from coming back, are usually not effective in treating MTC. Although, new treatments are being investigated in clinical trials and two chemotherapy medications, Vandetanib and Cabozantinib, have recently been approved by the FDA for use by patients with MTC. Radiation is sometimes used in patients with MTC after surgery is performed.
Nearly 90 percent of patients with MTC will live at least five years following their diagnosis. The 10-year survival rate drops to about 65 percent.
MTC treatment and accompanying survival rates can be complicated when the cancer spreads to other parts of the body. There is also a possibility that the parathyroid glands may accidentally be removed during surgery. The parathyroid glands are different from the thyroid in that they produce parathyroid hormone (PTH). Without these glands, patients can develop various parathyroid disorders.
Victoza and Pancreatitis
Pancreatitis occurs when the pancreas swells and becomes inflamed. Severe cases of pancreatitis require hospitalization and may be fatal. Victoza has not been studied in patients who have a history of pancreatitis, but the medication guide warns that pancreatitis is one of the severe side effects. The Institute for Safe Medication Practices (ISMP) reported that within the first nine months after Victoza’s approval, the FDA received reports of more than 100 cases of acute pancreatitis and pancreatitis linked to the drug.
Only one other drug in the same class has more reported cases of pancreatitis: Byetta. The ISMP contacted Novo Nordisk about its findings, and the company responded by pointing out that people with diabetes already have a 2.8-4.2 times higher risk of pancreatitis than those without diabetes. Furthermore, the company said it already has an FDA-approved plan to educate patients and doctors about the risks of Victoza, including pancreatitis.
According to the FDA safety alert posted in June 2011, Novo Nordisk reported more patients suffered from pancreatitis while taking Victoza in clinical trials than patients treated with comparable drugs. According to a 2012 study by Franks et al. published in the Annals of Pharmacotherapy, a literature survey found 11 cases of pancreatitis reported from patients taking Victoza, with one case resulting in death.
In March 2013, the FDA announced it had received data from unpublished studies pointing to a possible link between pancreatic cancer and drugs like Victoza, Januvia and Byetta.
Treatment of Pancreatitis and Signs to Watch Out For
Treatment with Victoza should be immediately discontinued in patients suspected of having pancreatitis. In patients diagnosed with the serious condition, the diabetes medication should not be restarted.
Treatment for pancreatitis often requires a hospital stay where pain medicines and IV fluids may be administered. Stopping foods and fluids by mouth may also be recommended in some patients to limit the activity by the pancreas. A tube can also be inserted through the nose and mouth to remove the contents of the stomach. This may be done when symptoms such as vomiting and severe pain do not improve.
- Persistent, severe abdominal pain usually felt in the upper left side or middle of the abdomen and sometimes radiating to the back
- Clay-colored stools
- Bloating and fullness
- Mild yellowing of the skin and whites of the eyes (jaundice)
- Swollen abdomen
Please seek the advice of a medical professional before making health care decisions.