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Januvia and Janumet Side Effects

Januvia and Janumet are similar medications used in the treatment of Type 2 diabetes that are linked to several serious side effects. Adverse reactions can come on suddenly and be severe, or even deadly. Some of the potential side effects include lactic acidosis, pancreatitis, including necrotizing pancreatitis, and certain types of cancers, including pancreatic and thyroid cancer.

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Antidiabetic drugs Januvia and Janumet are used to treat Type 2 diabetes, a life-long disease characterized by a high level of sugar (glucose) in the blood. Complications of diabetes can include stroke, kidney disease, high blood pressure, foot problems and other problems.

But medications used to treat the chronic condition can have risks of their own. Some Januvia and Janumet side effects are associated with active ingredient sitagliptin. Others are linked to metformin, a secondary active ingredient in Janumet.

These serious side effects that can cause permanent injury and/or possible death include:
  • Lactic acidosis
  • Pancreatitis, including necrotizing pancreatitis
  • Certain cancers, including pancreatic cancer and thyroid cancer
Other potentially serious side effects listed in the warnings and precautions section of the drugs’ labeling include:
  • Heart failure
  • Kidney impairment
  • Decreased vitamin B-12 levels
  • Change in clinical status in patients with previously controlled Type 2 diabetes
  • Hypoglycemia when used in conjunction with other medications known to lower blood glucose levels
  • Loss of control of blood glucose
  • Hypersensitivity (allergic) reactions
  • Severe and disabling joint pain (arthralgia)
  • Skin disorder characterized by large blisters (bullous pemphigold)

Lactic Acidosis

Post-marketing reports have linked metformin use to the development of lactic acidosis in patients. Metformin is one of two active ingredients found in Janumet. Some of these cases of metformin-associated lactic acidosis have resulted in the following health complications in patients. These potentially fatal conditions include low body temperature (hypothermia), low blood pressure (hypotension) and resistant bradyarrhythmias (abnormally slow heart rate).

Metformin-associated lactic acidosis is characterized by elevated blood lactate levels, or the amount of lactic acid in the blood. Metformin interferes with the liver’s reabsorption of lactate, which results in these raised lactate blood levels and increases a patient’s risk of developing lactic acidosis. This risk is especially high for patients more susceptible to the serious condition, meaning those with certain risk factors for lactic acidosis.

Risk factors for metformin-associated lactic acidosis include:
  • Kidney impairment
  • Metformin-use (such as Janumet) along with the use of other certain drugs (like carbonic anhydrase inhibitors, such as topiramate used to treat seizures in adults or children with epilepsy, as well as for the prevention of migraine headaches)
  • Being 65 or older
  • Having a radiological study (such as an X-ray) with contrast (dye), surgery or other procedures
  • Hypoxic states (such as acute congestive heart failure), where the body or a region of the body is deprived of needed oxygen supply to the tissues
  • Excessive alcohol use
  • Liver impairment

What Is Lactic Acid?

Lactic acid is a substance in the body primarily produced in muscle cells and red blood cells. It forms when the body breaks down carbohydrates for fuel when oxygen levels are too low to adequately support energy production. Oxygen levels in the body can drop during intense or prolonged exercise or when infection or disease is present.

Lactate production during extreme exertion is thought to be a natural defense mechanism responsible for slowing key systems in the body needed to maintain muscle use and thereby preventing permanent damage.

When lactate is produced, it results in the burning sensation often felt during prolonged exercise. This pain is meant to trigger the brain to stop overworking the body and allow for a period of recovery to clear the lactic acid.

When lactic acid builds up in the bloodstream faster than it can be removed, such as in instances of intense exercise, severe illness or disease, such as cancer or sepsis (severe infection affecting the whole body), or with the use of certain medications such as Janumet, lactic acidosis occurs. Having lactic acidosis means body tissues are not getting enough oxygen.

Symptoms of Lactic Acidosis

The onset of metformin-associated lactic acidosis is often subtle.

  • Malaise, or a general feeling of discomfort, illness or uneasiness
  • Muscle pain
  • Respiratory distress
  • Somnolence, or a state of strong desire for sleep, or sleeping for unusually long periods of time
  • Abdominal pain

As the condition progresses, patients might experience nausea and weakness.

Treatment of Lactic Acidosis

Modern Hemodialysis Machine
Hemodialysis machines filter blood outside the body

When metformin-associated lactic acidosis is suspected in patients taking Janumet, the diabetes drug should be immediately discontinued, according to drug labeling. Check with your doctor when making health care decisions. Supportive measures to treat affected patients should be promptly performed in a hospital setting.

Hemodialysis, using a machine and other devices to filter blood outside of your body, is the recommended treatment to fix acidosis and remove excess metformin.

Pancreatitis and Necrotizing Pancreatitis

There have been post-marketing reports of patients developing acute (sudden and severe) pancreatitis after taking Januvia and Janumet. Some of these cases resulted in death from hemorrhagic or necrotizing pancreatitis.

Did You Know?
Pancreatitis in patients taking Januvia or Janumet has resulted in death in some cases.

Pancreatitis is an inflammation of the pancreas. It causes the body’s digestive enzymes to attack the pancreas. In severe cases, the disease can cause tissue damage, infection, cyst formation and bleeding. The damage can spread to other organs like the heart, kidneys and lungs, and the mortality rate is 10 to 30 percent.

Acute pancreatitis

Cases of pancreatitis associated with Januvia and Janumet tend to be acute, meaning the disease occurs quickly. It can be fatal. A UCLA clinical study published in the journal Gastroenterology revealed that taking Januvia increases the risk of pancreatitis six-fold and cases usually develop in less than two months.

Nearly 100 cases of acute pancreatitis caused by Januvia, including necrotizing pancreatitis, were reported to the FDA between 2006 and 2009. Necrotizing pancreatitis occurs when digestive hormones produced by the pancreas begin to digest the pancreatic tissue, killing it. This can lead to serious infection and death.

Safety Alerts

In 2009, the FDA issued a safety alert that linked sitagliptin, the active ingredient in Januvia and Janumet, to acute pancreatitis.

Pancreatitis can also lead to pancreatic cancer. The FDA issued an updated alert in 2013, saying it was still investigating Januvia and similar drugs for evidence that they caused pancreatitis or pancreatic cancer.

According to a study published in February 2013 in JAMA Internal Medicine, patients taking Januvia or Byetta were twice as likely as those who took other drugs to end up in the hospital with pancreatitis that can be fatal. Research found that the inflammation results from pancreatic lesions caused by the drugs.

Symptoms of Pancreatitis

Acute pancreatitis occurs suddenly and without much warning. It often starts with pain felt in the upper left side or middle of the abdomen. This pain can get worse within minutes of eating or drinking, especially when eating foods with a high fat content. It is also typically constant and more severe than general abdominal pain, and lasts for several days. Lying flat on one’s back might also cause the pain to worsen. The pain can spread (radiate) to the back or below the left shoulder blade.

Other symptoms of pancreatitis can include nausea and vomiting. Patients with the condition will often look ill and have a fever. Patients with pancreatitis may also experience several other symptoms as the disease progresses. These conditions may include clay-colored stools, gaseous abdominal fullness, sweating, hiccups, indigestion and mild yellowing of the skin and white of the eyes (jaundice, or high bilirubin levels).

Necrotizing pancreatitis happens when acute pancreatitis is left untreated or improperly treated. Symptoms of necrotizing pancreatitis are similar to those experienced by patients with acute pancreatitis, and might also include dehydration and rapid heart rate.

Treatment of Pancreatitis

Treatment of acute pancreatitis usually involves several days of hospitalization and intravenous (IV) fluids, antibiotics and other medicines for pain relief. Stopping food or fluid by mouth will also help to relieve pancreatic activity, thereby alleviating the worsening of symptoms.

In some cases, a tube may need to be inserted through the nose or mouth to remove the contents of the stomach. This procedure is called nasogastric suctioning. This is typically the go-to treatment when symptoms of vomiting and severe pain do not improve, or if a paralyzed bowel develops (a condition called paralytic ileus). The tube will likely need to stay in place for one to two days up to one to two weeks.

In the most severe cases, surgery may be needed to remove the damaged, dead or infected pancreatic tissue. This is often done using a catheter or endoscopic procedure. However, if minimally invasive surgery is not effective, or recommended, open surgery will be needed as an alternative.

Pancreatic Cancer

Januvia and Janumet are also linked to pancreatic cancer. Pancreatic tumors can grow without symptoms and may not be detected until the cancer reaches a later stage. People taking sitagliptin have more than double the risk of developing pancreatic cancer, according to a UCLA study. The risk of developing cancer increases the longer someone takes Januvia or Janumet.

Twice the risk
The risk of developing pancreatic cancer is more than doubled in patients taking Januvia or Janumet.

Dr. Peter Butler, the study’s lead investigator, said it can be difficult to discover the extent of the damage done to the pancreas without removing it and examining it. As a result, pancreatic cancer may be diagnosed late. The American Cancer Society says the average rate of survival for pancreatic cancer is 18 to 20 months, and the overall five-year survival rate is 4 percent.

Thyroid Cancer

There have also been reports of patients developing thyroid cancer after taking Januvia. The UCLA study found a very minor increase in thyroid cancer, with only two cases reported out of the sample group. The 2015 analysis of FDA adverse event reports also found an increase in thyroid cancer in people who took incretin-based therapies like Januvia, although glucagonlike peptide-1 (GLP-1) receptor agonists like Victoza had a much higher incidence of thyroid cancer.

According to the American Cancer Society, the death rate of thyroid cancer is relatively low compared to other cancers. However, it can cause many serious side effects including swelling of the neck, pain, voice changes and hoarseness, trouble swallowing or breathing, and a constant cough.

Cancer Symptoms

Symptoms of cancer can vary, depending on where the cancer starts in the body, how big it is, if it has spread (metastasized), and how much it affects the body’s organs or tissues.

3D illustration of cancer cells in the process of mitosis
Cancer cells use up a lot of the body's energy stores

Cancers of all kinds may cause some general signs and symptoms such as extreme tiredness (fatigue), fever, pain or unexplained weight loss. When these symptoms persist, it may be related to cancer. Cancer cells use up much of the body’s energy stores and can also release substances that may alter the way the body makes or gets energy from food.

When cancer affects a critical part of the body or organ, such as the brain, even smaller tumors can cause symptoms. But other types of cancer, such as pancreatic cancer, may not cause symptoms until it grows large enough to crowd nearby organs (causing stomach pain) or press on adjacent nerves (causing back pain).

For this reason, pancreatic cancer is difficult to detect early. With the gland being located deep within the body, tumors are also hard to see or feel during routine exams. Additionally, patients have very few, if any, symptoms of the cancer until it has already begun to spread.

By the time the cancer becomes apparent, patients might experience the following symptoms:
  • Jaundice (yellowing of the skin) Belly or back pain
  • Weight loss and poor appetite
  • Nausea and vomiting
  • Gallbladder or liver enlargement
  • Blood clots
  • Fatty tissue abnormalities
  • Diabetes (high blood sugar)

Symptoms of Thyroid Cancer

Most thyroid cancers are found early when neck lumps or nodules become apparent. However, not all lumps in the thyroid are cancerous. But other signs and symptoms accompanying a lump or swelling in the neck may indicate thyroid cancer or other cancers of the neck area.

3D rendering of thyroid cancer
Signs and symptoms of thyroid cancer might include:
  • A lump in the neck, sometimes growing quickly
  • Swelling in the neck
  • Pain in the front of the neck, sometimes radiating (spreading) up to the ears
  • Hoarseness or other voice changes that do not improve or go away
  • Trouble swallowing
  • Trouble breathing
  • A constant cough that is not due to a cold or other chronic health condition, such as asthma

Cancer Treatments

Although surgery to remove the cancer is usually the first line of treatment, several other options are available, including:
Chemotherapy
use of medications to treat cancer
Radiation therapy
use of radiation to shrink early-stage cancer, prevent cancer from coming back or treat symptoms when cancer has spread
Targeted therapy
newer form of treatment that uses drugs to target and attack cancer cells
Immunotherapy
treatment that uses the body’s own immune system to fight off the cancer

Survival rates for pancreatic cancer are relatively low. The best-case scenario for stage I cancer, depending on the part of the pancreas affected, is anywhere from 14 percent to 61 percent. However, pancreatic cancer is rarely found early on.

In individuals diagnosed with pancreatic cancer who did not have the tumors surgically removed, the five-year survival rate was found to be at just 16 percent.

Treatment of Thyroid Cancer

Survival rates for patients diagnosed with thyroid cancer are much more promising, with stage I and stage II cancers near 100 percent. All survival rates for each stage of various thyroid cancers are 50 percent or higher, except for those diagnosed with stage IV medullary thyroid cancer. Other cancer procedures include radioactive iodine treatment, thyroid hormone therapy and external beam radiation therapy using high-energy rays to destroy cancer cells or slow their growth.

Please seek the advice of a medical professional before making health care decisions.

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14 Cited Research Articles

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