Nesina (alogliptin), Kazano (alogliptin and metformin hydrochloride) and Oseni (alogliptin and pioglitazone) are oral drugs developed by Japan-based Takeda Pharmaceuticals, Inc. Its partner, Furiex 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. Nesina would have been the first DPP-4 drug released in the U.S. But because the FDA had questions about the drug’s cardiovascular safety, Takeda was forced to conduct new safety trials before the drug could be approved.
Nesina (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.
The new alogliptin-based medicines have made millions for Takeda. In 2016, the company reported that Nesina made about $449 million in the U.S.
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.
What Do Nesina, Kazano & Oseni Treat?
Nesina, Kazano and Oseni are indicated in the treatment of Type 2 diabetes. This serious health condition is characterized by the presence of high levels of glucose, or sugar, in the blood. In patients with Type 2 diabetes, this metabolic abnormality is caused by either a lack of insulin production or the body’s inability to use the insulin properly.
What Is Diabetes?
There are two main types of diabetes – Type 1 and Type 2. Type 1 diabetes differs from Type 2 in that it usually develops during childhood, or at a young age, whereas Type 2 diabetes tends to appear most often in middle-aged and older adults. Type 1 diabetes is caused by damage to the pancreas.
The pancreas is a flat, elongated organ located deep within the abdomen behind the stomach. It is important in digestion and blood sugar regulation. Enzymes produced by the pancreas assist in digesting proteins, fats and carbs, while hormones, also produced by the pancreas and known as insulin and glucagon, help to maintain appropriate levels of glucose (sugar) in the blood.
Insulin is responsible for decreasing blood sugar levels by allowing the body’s cells to use the glucose for energy. Contrarily, glucagon raises blood sugar levels. Therefore, the combination of the two work together to maintain the proper amount of sugar in the blood.
However, when the pancreas is damaged, the organ may be unable to produce a sufficient amount of insulin, or none at all. This results in a diagnosis of Type 1 diabetes.
Nesina, Kazano & Oseni Not Approved to Treat Type 1 Diabetes
Nesina, Kazano and Oseni are not FDA-approved to treat Type 1 diabetes. Nor are the medications indicated to treat ketoacidosis, which is a potentially deadly problem that can affect people with diabetes and possibly lead to what is referred to as a diabetic coma.
Type 2 diabetes is much more common than Type 1, affecting about 90 percent of patients who have diabetes, according to the National Institutes of Health (NIH).
How Do Nesina, Kazano & Oseni Work?
Like other DPP-4 drugs, Nesina, Kazano and Oseni block DPP-4, an enzyme 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 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.
In clinical trials for Nesina, researchers gathered data from 14,778 patients with Type 2 diabetes. The average age of trial participants was 58 years old and they used Nesina for 49 weeks. About 3,348 patients used the drug for more than a year.
- Nasopharyngitis (common cold)
- Upper respiratory tract infection
- Joint pain
- Kidney problems
- Allergic reactions
- Stevens-Johnson syndrome (severe skin reaction)
- Inflammation and swelling
- Bullous pemphigoid (skin condition with large, fluid-filled blisters)
Additional Side Effects and Black Box for Kazano
In addition to safety concerns related to alogliptin and 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.
- Back pain
- Urinary tract infections
- Abdominal discomfort
Additional Side Effects and Black Box for 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 because of Actos.
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.
Safety Issues Found in Postmarket Studies
In clinical studies done after the drugs hit the market, 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 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 post-marketing surveillance by the FDA for its safety regarding use in children, heart safety, liver abnormalities, pancreatitis and severe hypersensitivity reactions.
Dosages & Strengths
Each dose of alogliptin and combination drug is different depending on the patient, especially if they have kidney problems. Because each patient may react differently to each medication, doctors may increase or decrease the dose after a patient begins treatment. In the case of Kazano and Oseni, these drugs use alogliptin in combination with varying strengths of metformin (Glucophage or Fortamet) and pioglitazone (Actos).
6.25 mg, 12.5 mg or 25 mg tablets of alogliptin taken once daily with or without food. Patients with moderate kidney disease should go no higher than a 12.5 mg dose. For patients with severe kidney disease, the lowest dose of 6.25 mg is recommended.
12.5 mg alogliptin/500 mg metformin and 12.5 mg alogliptin/1000 mg metformin. Patients should take Kazano twice daily with food. Patients with severe kidney problems should not use Kazano.
25 mg alogliptin/15, 30 & 45 mg pioglitazone and 12.5 mg alogliptin/15, 30 & 45 mg pioglitazone. No dose of Oseni is safe for patients with severe renal impairment. Patients take Oseni once daily with food.
While researchers did not observe any drug interactions in clinical trials with alogliptin, Kazano and Oseni contain metformin and pioglitazone. These two medications have their own set of drug interactions. Kazano metformin interactions include: Alcohol, insulin, topiramate, zonisamide, estrogens, oral contraceptives, thyroid drugs. Oseni pioglitazone interactions include: Gemfibrozil and other CYP2C8 inhibitors.
Please seek the advice of a medical professional before making health care decisions.