Nesina (alogliptin), Kazano (alogliptin and metformin hydrochloride) and Oseni (alogliptin and pioglitazone) are oral drugs developed by Japan-based Takeda Pharmaceuticals, Inc. Its partner, Fuirex Pharmaceuticals, markets the drugs. All three drugs were approved in 2010 in Japan and then in January 2013 by the U.S. Food and Drug Administration (FDA). Along with diet and exercise, Nesina, Kazano and Oseni help control blood sugar in people with Type 2 diabetes. The drugs are not intended for use in patients with Type 1 diabetes or ketoacidosis.
The main active ingredient in all three medications is alogliptin, a drug that belongs to a class of medications called dipeptidyl peptidase-4 (DPP-4) inhibitors. Drugs in this class help stimulate the release of more insulin after a meal to control blood sugar. Other drugs in the class include Januvia, Tradjenta, Onglyza and Kombiglyze XR. Takeda intended Nesina to be the first DPP-4 drug to be released in the U.S. But because the FDA issued stricter cardiovascular safety requirements, Takeda was forced to conduct new safety trials before the drug could be approved.
Alogliptin is Takeda's follow-up medication to its blockbuster diabetes drug, Actos (pioglitazone). At the height of its sales in 2011, Actos sales topped out at $4.5 billion worldwide and made up 27 percent of the company’s revenue. The patent on Actos expired in August 2012, but Takeda is using Actos (pioglitazone) in combination with alogliptin in its new medicine, Oseni.
Studies have shown that drugs in the DPP-4 class are effective at controlling blood sugar, but other studies have linked them to serious side effects like pancreatitis and possible pancreatic cancer. A number of people who took these drugs filed lawsuits against the drugs' manufacturers.
Nesina, Kazano and Oseni are Type 2 diabetes drugs manufactured by Takeda Pharmaceuticals. These medications are linked to side effects, including heart failure, pancreatitis and cancer.
How Do Nesina, Kazano & Oseni Work?
Like other DPP-4 drugs, Nesina, Kazano and Oseni block DPP-4, an enzyme that is responsible for degrading the incretin hormone, glucagon-like peptide-1 (GLP-1). GLP-1 encourages the pancreas to secrete insulin after meals. It also regulates how much sugar the liver produces.
By blocking DPP-4 from breaking down GLP-1 in people with Type 2 diabetes, alogliptin allows GLP-1 to remain in the blood longer. This allows the pancreas to secrete more insulin and the liver to produce less sugar. This helps control blood sugar.
Kazano and Oseni are combination drugs, and they also help control blood sugar in people for whom alogliptin alone is not effective.
Kazano combines alogliptin with metformin. In addition to controlling blood sugar by blocking DPP-4, the metformin in Kazano reduces the amount of sugar absorbed into the blood from the intestines, reduces the amount of sugar produced by the liver and makes the body more sensitive to insulin.
Oseni combines alogliptin with Actos (pioglitazone). Like Nesina and Kazano, Oseni also blocks DPP-4, and pioglitazone works by increasing the body's sensitivity to insulin.
Serious Side Effects
In clinical studies, DPP-4 inhibitors were linked to a number of side effects. Some are rare and severe, like pancreatitis. More common side effects include stomachaches and nausea.
In an article by Elashoff et al published in the July 2011 Issue of Gastroenterology, researchers suggest that inhibition of DPP-4 compromises the immune system and makes the body susceptible to all types of cancer.
Alogliptin is also still under postmarketing surveillance by the FDA for its safety regarding use in children, heart safety, liver abnormalities, pancreatitis and severe hypersensitivity reactions.
After taking Nesina, Kazano or Oseni, people reported postmarketing cases of acute pancreatitis, a condition where the pancreas become inflamed and swollen. In severe cases, this can lead to hospitalization and even death.
Researchers at Johns Hopkins University reported that people who took DPP-4s were twice as likely to suffer from pancreatitis that required hospitalization.
|According to the drugs' precautions and warnings, the following conditions predispose patients to pancreatitis:
Controversy still exists over whether DPP-4s can cause pancreatic cancer, and both the FDA and European Medicines Agency say not enough evidence exists to support this link.
In one study by Alexandra Butler and colleagues published in Diabetes, the researchers examined the pancreases of organ donors who were using DPP-4s and other incretin-based therapies. Researchers found abnormal cells "with the potential for evolution into neuroendocrine tumors."
A recent study by researchers at Brigham and Women's Hospital in Boston showed that Nesina did not increase heart attack risk. However, doctors also determined that DPP-4s may increase the risk of heart failure.
Additional Side Effects of Kazano
In addition to safety concerns related to DPP-4s, Kazano also has a black-box warning for lactic acidosis, a potential side effect of metformin. It is a rare but serious condition caused by the buildup of lactic acid in the blood and requires immediate medical care.
|Signs of lactic acidosis include:
Additional Side Effects of Oseni
Because Oseni is a combination of alogliptin and pioglitazone, it can have a combination of side effects. In addition to pancreatic abnormalities, this drug also carries the risk of bladder cancer.
In clinical trials of pioglitazone, researchers found tumors in male rats. Other studies suggest that taking pioglitazone increases the risk of bladder cancer by 83 percent.
Pioglitazone also increases the risk of edema and weight gain. In women, abnormal ovulation can occur, which can increase the possibility of pregnancy.
Oseni has a black-box warning for congestive heart failure and should not be used in people with a history of heart failure.
Other Side Effects
|Some of the more common side effects associated with these drugs include:
Nesina, Kazano & Oseni Lawsuits
People who took DPP-4 medications like Nesina, Kazano and Oseni filed lawsuits against the manufacturers of the drugs after developing pancreatic cancer. Plaintiffs claim the manufacturers were negligent, manufactured a defective product and did not properly warn the public of the risks of the drugs.
People who took Nesina, Kazano or Oseni and developed pancreatic cancer or suffered serious side effects like heart failure or lactic acidosis may file lawsuits in the future.