FDA Rejects Application for Onglyza Combo Drug

Onglyza (saxagliptin) is a type 2 diabetes medication that was approved by the FDA in 2009. It belongs to a class of drugs known as “incretin mimetics,” which stimulate the pancreas to make more insulin after the patient eats a meal, in order to keep blood sugar levels stable.

According to a recent press release put out by Onglyza’s co-manufacturer, AstraZeneca, the FDA recently rejected their application for a new drug that combines Onglyza with dapagliflozin (Farxiga), which is also manufactured by AstraZeneca and Bristol-Myers Squibb. The FDA stated that they needed to see more clinical data to establish the drug as safe and effective.

FDA Requires More Clinical Data on Combo Diabetes Drug

Other companies have already put out combination drugs like this one, combining so-called “DPP-4 inhibitors” like Onglyza with “SGLT2 inhibitors” like Invokana and Farxiga. Manufacturers Eli Lilly and Boehringer Ingelheim, for example, released “Glyxambi” in January 2015.

DDP-4 inhibitors work by increasing hormones that stimulate the pancreas to produce more insulin, while also stimulating the liver to produce less glucose. SGLT2 inhibitors work by blocking the reabsorption of glucose by the kidneys, causing almost all to be flushed out of the body via the urine.

Both of these classes of drugs have been linked to safety concerns, which may explain why the FDA was more cautious with this new combination product proposed by AstraZeneca. The administration asked for additional data, which may require the manufacturer to conduct additional studies. AstraZeneca stated they will work closely with the FDA “to determine the appropriate next steps,” and that they remain committed to the development of this combination drug.

DDP-4 Inhibitors Associated with Risk of Heart Failure and Pancreatitis

It was nearly two years ago that the FDA issued a drug safety communication stating that they had requested additional trials on Onglyza, as well, after the large clinical trial (the SAVOR study) reported that patients taking the drug had a 27 percent increased risk of being hospitalized for heart failure, compared to those taking placebo.

An FDA advisory panel later recommended that Onglyza and other similar drugs should carry warnings about their potential to increase risk of heart failure. Watchdog group Public Citizen also warned about the drug’s potential side effects in their “Worst Pills Best Pills” newsletter, and has already placed another DDP-4 inhibitor drug, Januvia, on their “do not use” list.

This class of drugs has also been linked to other possible risks, including pancreatitis and pancreatic cancer.

SGLT2 Inhibitors Associated with Risk of Kidney Problems and Ketoacidosis

The other half of AstraZeneca’s proposed combo pill is an SGLT2 inhibitor. This class of drugs has also been associated with significant health risks, including kidney impairment and kidney failure, urinary tract infections, bone health problems, and diabetic ketoacidosis (DKA).

The FDA warned about DKA associated with these drugs in May 2015, after reports surfaced of patients with type 2 diabetes taking these drugs and being hospitalized for the condition. DKA is a potentially dangerous medical issue in which the blood becomes too acidic, and without immediate treatment can result in coma and even death. The FDA warned patient and doctors to be on the lookout for symptoms like nausea and vomiting, difficulty breathing, unusual fatigue, and abdominal pain.