- 1 Onglyza and Kombiglyze XR are Type 2 diabetes medications sold by AstraZeneca and Bristol-Myers Squibb. Medications like these are linked to an increased risk of pancreatitis and possibly cancer.
- 2 How Do Onglyza & Kombiglyze XR Work?
- 3 Serious Side Effects
- 4 Onglyza and Kombiglyze XR Lawsuits
Onglyza is a popular medication, partly because it effectively controls blood sugar and does not encourage weight gain like other diabetes medications. The drug made $709 million in 2012, and analysts say that by 2018, annual sales of the drug could skyrocket to $2.47 billion. Kombiglyze XR contains the same active ingredient as Onglyza, but it incorporates metformin with saxagliptin and is an extended release pill.
These medications belong to a group of Type 2 diabetes medications called incretin-based therapies. Specifically, they belong to a class of drugs called DPP-4 inhibitors. These medicines help the pancreas secrete more insulin and stop the liver from making excess sugar.
According to British Medical Journal editor Deborah Cohen, when DPP-4 drugs first appeared on the market, they were “touted as the ‘new darlings of diabetes treatment’ – the biggest breakthrough since the discovery of insulin nearly a hundred years before.” Along with related GLP-1 drugs Byetta and Victoza, DPP-4s are widely prescribed.
However, some doctors are concerned by reports of a possible increased risk of pancreatitis (inflammation of the pancreas) and pancreatic and thyroid cancer associated with incretin-based therapies. Hundreds who took these drugs filed lawsuits against the drugs’ makers after they developed pancreatitis or pancreatic cancer, claiming that the drug companies failed to warn of the risk.
In April 2015, an FDA panel said that Onglyza should carry a warning about the increased risk of heart failure. Data from the SAVOR study involving 16,000 patients found that people who took Onglyza had a 27 percent greater risk of heart failure hospitalizations than those in the control group.
How Do Onglyza & Kombiglyze XR Work?
The active ingredient in Onglyza is saxagliptin, which is a DPP-4 inhibitor. DPP-4 is an enzyme that naturally occurs in the body. Its job is to break down an incretin hormone called GLP-1. After eating, GLP-1 is released into the blood and signals the pancreas to make insulin.
In people with diabetes, GLP-1 secretion is reduced, which causes the pancreas to produce less insulin, resulting in too much sugar in the blood. Since DPP-4 breaks down GLP-1, inhibiting DPP-4 allows GLP-1 to remain in the body longer. This signals the pancreas to make more insulin after meals.
In addition to producing too little insulin, the pancreases of people with Type 2 diabetes also release too much glucagon, a hormone that tells the liver to produce more glucose.
Onglyza reduces blood sugar in two ways:
- Reduce the amount of glucagon secreted by the pancreas, stopping the the liver from making too much glucose.
- Help the body produce more insulin after meals.
|Kombiglyze XR also contains metformin, so it helps reduce blood sugar in four ways:|
|Decrease sugar absorbed in the gut||Reduce sugar made by liver|
|Make the body more sensitive to insulin||Increase amount of insulin produced after meals|
Serious Side Effects
Onglyza and Kombiglyze XR are both linked to serious side effects. Most notably, a number of 2013 studies raised concern about DPP-4 drugs and their link to abnormal pre-cancerous cells in the pancreas. There is also evidence that may point to an increased risk of heart failure.
One of the most serious complications linked to Onglyza and other incretin therapies is the possibility of an increase in the risk of pancreatic cancer, a cancer that is difficult to treat because it is often not diagnosed until later stages.
One of the latest studies by Butler et al., published in the March 2013 issue of Diabetes, found pre-cancerous cells in the autopsied pancreases of people taking incretin drugs.
According to the study, one of the claims of DPP-4 drugs is that they increase the number and size of beta cells in the pancreas – cells that are responsible for secreting insulin. In people with Type 2 diabetes, the beta cells shrink or die and lose their ability to produce insulin.
Butler and colleagues found that that the drugs did indeed increase the number of beta cells, but that the cells were abnormal. They also found small, benign tumors called adenomas that can become malignant.
One of the key findings was that this change only occurred in Type 2 diabetes patients who took DPP-4 or GLP-1 drugs, and not in people with diabetes who took other drugs.
The European Medicines Agency (EMA) reacted by saying that the current evidence is not sufficient to prove a definitive link between these drugs and pancreatic cancer; however, regulators continue to monitor the situation. The FDA investigated the claims, but after the EMA released its decision, the U.S. agency took a similar position.
In November 2011, information about pancreatitis was added to Onglyza’s warnings and precautions. Pancreatitis is inflammation of the pancreas; serious cases require hospitalization and can lead to death. Pancreatitis can also lead to pancreatic cancer.
The FDA received postmarket reports of patients suffering from acute pancreatitis after taking Onglyza.
According to the FDA, doctors should carefully monitor patients, and Onglyza and Kombiglyze XR should be discontinued if pancreatitis is suspected. It is unknown whether Onglyza increases the risk of a relapse in patients who have a history of pancreatitis.
In addition to abnormalities in the pancreas, a September 2013 study found a possible link between Onglyza and an increase in heart failure. The goal of the 16,492-patient study was to see if Onglyza could provide heart-protective benefits in addition to controlling blood sugar.
Researchers did not find any evidence that the drug could protect the heart, though the drug did not contribute to heart attacks. But, they found a slight increased risk for heart failure.
Dr. Anthony DeMaria, editor in chief of the Journal of the American College of Cardiology, told Reuters that the drug should probably be avoided by people at risk for heart failure.
Side Effects of Kombiglyze XR
Because Kombiglyze XR combines the active ingredient of Onglyza with metformin, people taking the drug should be aware that this drug carries the same risks as Onglyza, but includes the possible complications of metformin as well.
The biggest concern with metformin is a condition called lactic acidosis. This is a rare side effect that causes a buildup of lactic acid in the blood and can cause death. Patients need immediate medical attention if this condition is suspected. Symptoms include weakness, fatigue, muscle pain, trouble breathing, vomiting and irregular heartbeat.
|Onglyza and Kombiglyze XR also carry the risk of more common side effects such as:|
|Nausea and vomiting||Stuffy or runny nose|
|Sore throat||Upper respiratory tract infection|
|Urinary tract infection||Low blood sugar|
|Swelling or fluid retention|
Patients taking Onglyza or Kombiglyze XR along with diabetes drugs in the thiazolidinedione (TZD) family, such as pioglitazone (Actos) or rosiglitazone (Avandia), are at an increased risk of swelling in the hands, feet or ankles.
Onglyza and Kombiglyze XR Lawsuits
Because of the possible increased risk of pancreatic cancer associated with drugs in the same class as Onglyza and Kombiglyze XR such as Januvia, people who were diagnosed with pancreatic cancer after taking these drugs filed lawsuits against the manufacturers.