Tradjenta & Jentadueto Side Effects
Tradjenta and Jentadueto both contain the active ingredient linagliptin to treat Type 2 diabetes. Common side effects of linagliptin include diarrhea, cough, sore throat, and runny or stuffy nose. Serious side effects include pancreatitis, skin reactions and joint pain.
Linagliptin is the active ingredient in two antidiabetic drugs made by Boehringer Ingelheim: Tradjenta and Jentadueto. Jentadueto combines linagliptin with metformin.
The most common side effects of linagliptin are minor and include runny nose, sore throat, diarrhea and cough, according to the Tradjenta Medication Guide. These side effects may change when combined with other antidiabetic drugs or insulin. When used with other diabetes drugs, the most common side effects are gastrointestinal problems.
- Urinary tract infection
- Weight gain
- Increased cholesterol
- Back pain
- Joint pain
- Upper respiratory infection
- Runny nose
- Pain in extremities
- Allergic reactions
- Increased uric acid
Jentadueto has these side effects plus those of metformin. The most common side effects of metformin are diarrhea, nausea and vomiting, flatulence, indigestion abdominal discomfort and headache.
After a drug hits the market, people may voluntarily report side effects or adverse events to the U.S. Food and Drug Administration. From 2011 to September 2018, the FDA’s Adverse Events Reporting System (FAERS) received 3,229 reports of adverse events for Tradjenta. Of these, 889 were serious and included 119 deaths. People reported 425 adverse events to FAERS for Jentadueto, including 12 deaths.
Overall, most studies show the drugs are safe and effective for most people. But, Jentadueto has a black box warning for lactic acidosis caused by metformin. Because metformin decreases the lactate processed by the liver, more of this compound stays in the blood and can be toxic. Symptoms of lactic acidosis include body pain, tiredness, respiratory distress, heart arrhythmias and low blood pressure.
Tradjenta and Jentadueto medication labels also warn about the risk of serious side effects, including inflammation of the pancreas (pancreatitis), hypoglycemia, joint pain and heart failure. Some people filed lawsuits against Boehringer Ingelheim claiming the company did not adequately warn about the risk of pancreatitis.
Studies on Pancreatitis
One of the biggest concerns for people who take Tradjenta or Jentadueto is pancreatitis. Inflammation of the pancreas can lead to hospitalization and turn fatal. The FDA has warned pancreatitis can be an issue with these drugs and others in the dipeptidyl peptidase 4 (DPP-4) inhibitors class.
People who took linagliptin during clinical trials reported pancreatitis upward four times more than those who took placebo (15.2 cases versus 3.7 cases in 10,000 patient years), according to Tradjenta and Jentadueto’s prescribing information.
An article published in the February 2017 issue of Diabetes Care found the risk of acute pancreatitis with DPP-4 inhibitor use was “rare but real.”
“We can conclude that pancreatitis is an established but rare side effect of DPP-4 inhibitors that occurs at a very low frequency,” the article said. “We should inform patients on this potential side effect.”
Authors J. Hans DeVries and Julio Rosenstock recommended running tests to rule out gallstones in patients with abdominal pain.
“In the linagliptin clinical trial program, pancreatitis occurred in 8 of 4,687 patients receiving linagliptin and in none of the 1,183 patients receiving placebo.”
Researchers have assessed the clinical safety of linagliptin in more than 4,000 patients with Type 2 diabetes, Maisha Kelly Freeman, doctor of pharmacy, reported in a 2011 article in Pharmacy and Therapeutics.
“In the linagliptin clinical trial program, pancreatitis occurred in 8 of 4,687 patients receiving linagliptin and in none of the 1,183 patients receiving placebo,” Freeman said.
A 2014 study by Dr. Michael Lehrke and colleagues found little to no pancreatic risk with linagliptin. Out of 4,810 patients, only two developed pancreatitis. There were no reports of precancerous lesions on the pancreas. Lehrke disclosed he had been a paid speaker for several drug companies, including Boehringer Ingelheim.
Cardiovascular Safety of Linagliptin
Tradjenta and Jentadueto carry warnings about the risk of heart failure. Boehringer Ingelheim added the warnings in 2017 after the FDA found Onglyza (saxagliptin) and Nesina (alogliptin), two other DPP-4 drugs, could increase the risk of heart failure.
“Heart failure can result in the heart not being able to pump enough blood to meet the body’s needs. As a result, we are adding new warnings to the drug labels about this safety issue,” the FDA said in a 2016 Drug Safety Communication.
“Heart failure can result in the heart not being able to pump enough blood to meet the body’s needs. As a result, we are adding new warnings to the drug labels about this safety issue.”
Prior to the warnings, Julio Rosenstock and colleagues had analyzed 19 clinical trials with a total of 9,459 participants to see if Tradjenta increased the risk of cardiovascular events, including heart failure. They found 12 people out of 5,847 who took linagliptin ended up in the hospital for heart failure versus 9 people in the placebo group.
They concluded linagliptin was not associated with an increase in cardiovascular risk, including heart failure.
It is important to note that Boehringer Ingelheim funded the study. The pharmaceutical industry funded most of the safety studies on linagliptin.
In addition, Rosenstock and colleagues said a limitation of their 2015 study was that patients only took linagliptin for 2.2 years and 1.5 years. This might not have been enough time to develop heart problems.
Severe Joint Pain
One of the latest warnings added to labels for Tradjenta, Jentadueto and other DPP-4 drugs is the risk of severe joint pain. According to an August 2015 FDA Drug Safety Communication, people have experienced joint pain in as little as one day after taking a DPP-4.
The FDA said it identified 33 cases of severe joint pain with DPP-4 use in its FAERS database over a seven-year period, but only two of those reports were associated with linagliptin specifically.
After the patients stopped taking the drugs, the symptoms vanished. Some people who re-started therapy with a DPP-4 experienced the symptoms again.
About a year after the FDA released its safety announcement, researchers in Japan published a study in Drug Target Insights that found no increase in joint pain among 20 people with advanced stage diabetic neuropathy who took linagliptin.
Still, Boehringer Ingelheim continues to warn that people who take the drugs may develop joint pain that can be severe. The drug maker advises people to call a doctor if they experience the side effect.
Another rare but serious side effect associated with DPP-4 drugs is a skin condition called bullous pemphigoid (BP) that can cause erosion and blisters.
The labels for Tradjenta and Jentadueto caution that the skin reaction may need to be treated in a hospital. Boehringer Ingelheim says to tell a doctor right away if someone who takes one of the drugs develops blisters.
In a 2018 Letter to the Editor in the journal of Cutaneous Immunology and Allergy, Dr. Junko Mukaijo and colleagues described a 64-year-old man who had been taking linagliptin for about six months and suffered blisters and lesions on his head, torso and limbs. He also had lesions in his mouth. Doctors diagnosed him with BP after taking a skin biopsy.
“According to the data, the proportional reporting ratio for linagliptin and [bullous pemphigoid] was the second highest after that for vildagliptin.”
In this case and other BP cases with linagliptin, stopping the drug cleared up the skin issues. Though, the man’s mouth lesions required steroid treatment.
“The number of reported cases of BP induced by linagliptin has been increasing during the past few years,” the authors wrote. “According to the data, the proportional reporting ratio for linagliptin and BP was the second highest after that for vildagliptin.”
Please seek the advice of a medical professional before making health care decisions.